Nicotinamide phosphoribosyltransferase: Difference between revisions

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(changed gene name to the one approved by the HUGO Gene Nomenclature Committee)
 
(I change that NAMPT do not activate the insulin receptor, since the original publication was retracted. Moreover, i add that NAMPT could bind to and activate TLR4 a recent article)
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'''Nicotinamide phosphoribosyltransferase''' (NAmPRTase or Nampt) also known as '''pre-B-cell colony-enhancing factor 1''' (PBEF1) or '''visfatin''' is an [[enzyme]] that in humans is encoded by the ''NAMPT'' [[gene]].<ref name="Samal_1994">{{cite journal | vauthors = Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I | title = Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor | journal = Mol. Cell. Biol. | volume = 14 | issue = 2 | pages = 1431–7 |date=February 1994 | pmid = 8289818 | pmc = 358498 | doi = | url = | issn = }}</ref> This protein is the rate-limiting enzyme in the [[Nicotinamide adenine dinucleotide]] (NAD+) [[salvage pathway]] that converts [[nicotinamide]] to [[nicotinamide mononucleotide]] in mammals to enable NAD+ biosynthesis.<ref name="Revollo2007">{{cite journal|vauthors=Revollo JR, Grimm AA, Imai S|title=The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/visfatin in mammals|journal=Curr Opin Gastroenterol|date=March 2007|volume=23|issue=2|pages=164-70|doi=10.1097/MOG.0b013e32801b3c8f|pmid=17268245}}</ref> NAMPT has also been reported to be a cytokine (PBEF) that promotes B cell maturation and inhibits [[neutrophil]] [[apoptosis]].
'''Nicotinamide phosphoribosyltransferase''' (NAmPRTase or Nampt) also known as '''pre-B-cell colony-enhancing factor 1''' (PBEF1) or '''visfatin''' is an [[enzyme]] that in humans is encoded by the ''NAMPT'' [[gene]].<ref name="Samal_1994">{{cite journal | vauthors = Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I | title = Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor | journal = Molecular and Cellular Biology | volume = 14 | issue = 2 | pages = 1431–7 | date = February 1994 | pmid = 8289818 | pmc = 358498 | doi = }}</ref> This protein is the rate-limiting enzyme in the [[Nicotinamide adenine dinucleotide]] (NAD+) [[salvage pathway]] that converts [[nicotinamide]] to [[nicotinamide mononucleotide]] in mammals to enable NAD+ biosynthesis.<ref name="Revollo2007">{{cite journal | vauthors = Revollo JR, Grimm AA, Imai S | title = The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/visfatin in mammals | journal = Current Opinion in Gastroenterology | volume = 23 | issue = 2 | pages = 164–70 | date = March 2007 | pmid = 17268245 | doi = 10.1097/MOG.0b013e32801b3c8f }}</ref> NAMPT has also been reported to be a cytokine (PBEF) that promotes B cell maturation and inhibits [[neutrophil]] [[apoptosis]].


== Expression & Regulation ==
== Expression & Regulation ==


NAMPT is downregulated by an increase of miR-34a in obesity via a 3'UTR functional binding site of NAMPT mRNA resulting in a reduction of NAD(+) and decreased [[Sirtuin 1|SIRT1]] activity.<ref name="pmid23834033">{{cite journal | vauthors = Choi SE, Fu T, Seok S, Kim DH, Yu E, Lee KW, Kang Y, Li X, Kemper B, Kemper JK | title = Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT | journal = Aging Cell | volume = 12 | issue = 6 | pages = 1062–72 |date=December 2013 | pmid = 23834033 | doi=10.1111/acel.12135}}</ref>
NAMPT is downregulated by an increase of miR-34a in obesity via a 3'UTR functional binding site of NAMPT mRNA resulting in a reduction of NAD(+) and decreased [[Sirtuin 1|SIRT1]] activity.<ref name="pmid23834033">{{cite journal | vauthors = Choi SE, Fu T, Seok S, Kim DH, Yu E, Lee KW, Kang Y, Li X, Kemper B, Kemper JK | title = Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT | journal = Aging Cell | volume = 12 | issue = 6 | pages = 1062–72 | date = December 2013 | pmid = 23834033 | doi = 10.1111/acel.12135 }}</ref>


== Reaction ==
== Reaction ==
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== Function ==
== Function ==
NAmPRTase catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, one step in the biosynthesis of [[nicotinamide adenine dinucleotide]]. The protein is an adipokine that is localized to the bloodstream and has various functions, including the promotion of vascular smooth muscle cell maturation and inhibition of neutrophil apoptosis. It also activates insulin receptor and has insulin-mimetic effects, lowering blood glucose and improving insulin sensitivity. The protein is highly expressed in visceral fat and serum levels of the protein correlate with obesity. This gene has a pseudogene on chromosome 10.<ref name="entrez">{{cite web | title = Entrez Gene: PBEF1 pre-B-cell colony enhancing factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10135| accessdate = }}</ref>
NAmPRTase catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, one step in the biosynthesis of [[nicotinamide adenine dinucleotide]]. The protein is an adipokine that is localized to the bloodstream and has various functions, including the promotion of vascular smooth muscle cell maturation and inhibition of neutrophil apoptosis. It also activates insulin receptor and has insulin-mimetic effects, lowering blood glucose and improving insulin sensitivity. However, the paper was retracted in 2007. The protein is highly expressed in visceral fat and serum levels of the protein correlate with obesity. This gene has a pseudogene on chromosome 10.<ref name="entrez">{{cite web | title = Entrez Gene: PBEF1 pre-B-cell colony enhancing factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10135| access-date = }}</ref><ref>{{Cite journal|last=Fukuhara|first=Atsunori|last2=Matsuda|first2=Morihiro|last3=Nishizawa|first3=Masako|last4=Segawa|first4=Katsumori|last5=Tanaka|first5=Masaki|last6=Kishimoto|first6=Kae|last7=Matsuki|first7=Yasushi|last8=Murakami|first8=Mirei|last9=Ichisaka|first9=Tomoko|date=2007-10-26|title=Retraction|url=https://www.ncbi.nlm.nih.gov/pubmed/17962537|journal=Science (New York, N.Y.)|volume=318|issue=5850|pages=565|doi=10.1126/science.318.5850.565b|issn=1095-9203|pmid=17962537}}</ref>
 
Recently, it has been demonstrated that NAMPT could bind to and activate TLR4. <ref>{{Cite journal|last=Garcia|first=Joe G. N.|last2=Liang|first2=Jie|last3=Wang|first3=Ting|last4=Yousef|first4=Mohammed|last5=Saadat|first5=Laleh|last6=Letsiou|first6=Eleftheria|last7=Sammani|first7=Saad|last8=Quijada|first8=Hector|last9=Siddiqui|first9=Shahid S.|date=2015-08-14|title=Unique Toll-Like Receptor 4 Activation by NAMPT/PBEF Induces NFκB Signaling and Inflammatory Lung Injury|url=https://www.nature.com/articles/srep13135|journal=Scientific Reports|language=en|volume=5|pages=13135|doi=10.1038/srep13135|issn=2045-2322}}</ref>


== Nomenclature ==
== Nomenclature ==
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== History ==
== History ==
Nampt/PBEF/visfatin was originally cloned as a putative [[cytokine]] shown to enhance the maturation of [[B cell]] precursors in the presence of [[Interleukin-7]] (IL-7) and [[stem cell factor]], it was therefore named “pre-B cell colony-enhancing factor” (PBEF).<ref name="Samal_1994"/> When the gene encoding the bacterial nicotinamide phosphoribosyltransferase (''nadV'') was first isolated in ''Haemophilus ducreyi'', it was found to exhibit significant homology to the mammalian PBEF gene.<ref name="pmid11157928">{{cite journal | vauthors = Martin PR, Shea RJ, Mulks MH | title = Identification of a plasmid-encoded gene from Haemophilus ducreyi which confers NAD independence | journal = J. Bacteriol. | volume = 183 | issue = 4 | pages = 1168–74 |date=February 2001 | pmid = 11157928 | pmc = 94989 | doi = 10.1128/JB.183.4.1168-1174.2001 | url = | issn = }}</ref> Rongvaux et al.<ref name="pmid12555668">{{cite journal | vauthors = Rongvaux A, Shea RJ, Mulks MH, Gigot D, Urbain J, Leo O, Andris F | title = Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis | journal = Eur. J. Immunol. | volume = 32 | issue = 11 | pages = 3225–34 |date=November 2002 | pmid = 12555668 | doi = 10.1002/1521-4141(200211)32:11<3225::AID-IMMU3225>3.0.CO;2-L | url = | issn = }}</ref> demonstrated genetically that the mouse PBEF gene conferred Nampt enzymatic activity and NAD-independent growth to bacteria lacking nadV. Revollo et al.<ref name="pmid15381699">{{cite journal | vauthors = Revollo JR, Grimm AA, Imai S | title = The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells | journal = J. Biol. Chem. | volume = 279 | issue = 49 | pages = 50754–63 |date=December 2004 | pmid = 15381699 | doi = 10.1074/jbc.M408388200 | url = | issn = }}</ref> determined biochemically that the mouse PBEF gene product encodes a Nampt enzyme, capable of modulating intracellular NAD levels. Others have since confirmed these findings.<ref name="pmid15947248">{{cite journal | vauthors = van der Veer E, Nong Z, O'Neil C, Urquhart B, Freeman D, Pickering JG | title = Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation | journal = Circ. Res. | volume = 97 | issue = 1 | pages = 25–34 |date=July 2005 | pmid = 15947248 | doi = 10.1161/01.RES.0000173298.38808.27 | url = | issn = }}</ref> More recently, several groups have reported the crystal structure of Nampt/PBEF/visfatin and they all show that this protein is a dimeric type II phosphoribosyltransferase enzyme involved in NAD biosynthesis.<ref name="pmid16783373">{{cite journal | vauthors = Wang T, Zhang X, Bheda P, Revollo JR, Imai S, Wolberger C | title = Structure of Nampt/PBEF/visfatin, a mammalian NAD+ biosynthetic enzyme | journal = Nat. Struct. Mol. Biol. | volume = 13 | issue = 7 | pages = 661–2 |date=July 2006 | pmid = 16783373 | doi = 10.1038/nsmb1114 | url = | issn = }}</ref><ref name="pmid16901503">{{cite journal | vauthors = Kim MK, Lee JH, Kim H, Park SJ, Kim SH, Kang GB, Lee YS, Kim JB, Kim KK, Suh SW, Eom SH | title = Crystal structure of visfatin/pre-B cell colony-enhancing factor 1/nicotinamide phosphoribosyltransferase, free and in complex with the anti-cancer agent FK-866 | journal = J. Mol. Biol. | volume = 362 | issue = 1 | pages = 66–77 |date=September 2006 | pmid = 16901503 | doi = 10.1016/j.jmb.2006.06.082 | url = | issn = }}</ref><ref name="pmid16783377">{{cite journal | vauthors = Khan JA, Tao X, Tong L | title = Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents | journal = Nat. Struct. Mol. Biol. | volume = 13 | issue = 7 | pages = 582–8 |date=July 2006 | pmid = 16783377 | doi = 10.1038/nsmb1105 | url = | issn = }}</ref>
Nampt/PBEF/visfatin was originally cloned as a putative [[cytokine]] shown to enhance the maturation of [[B cell]] precursors in the presence of [[Interleukin-7]] (IL-7) and [[stem cell factor]], it was therefore named “pre-B cell colony-enhancing factor” (PBEF).<ref name="Samal_1994"/> When the gene encoding the bacterial nicotinamide phosphoribosyltransferase (''nadV'') was first isolated in ''Haemophilus ducreyi'', it was found to exhibit significant homology to the mammalian PBEF gene.<ref name="pmid11157928">{{cite journal | vauthors = Martin PR, Shea RJ, Mulks MH | title = Identification of a plasmid-encoded gene from Haemophilus ducreyi which confers NAD independence | journal = Journal of Bacteriology | volume = 183 | issue = 4 | pages = 1168–74 | date = February 2001 | pmid = 11157928 | pmc = 94989 | doi = 10.1128/JB.183.4.1168-1174.2001 }}</ref> Rongvaux et al.<ref name="pmid12555668">{{cite journal | vauthors = Rongvaux A, Shea RJ, Mulks MH, Gigot D, Urbain J, Leo O, Andris F | title = Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis | journal = European Journal of Immunology | volume = 32 | issue = 11 | pages = 3225–34 | date = November 2002 | pmid = 12555668 | doi = 10.1002/1521-4141(200211)32:11<3225::AID-IMMU3225>3.0.CO;2-L }}</ref> demonstrated genetically that the mouse PBEF gene conferred Nampt enzymatic activity and NAD-independent growth to bacteria lacking nadV. Revollo et al.<ref name="pmid15381699">{{cite journal | vauthors = Revollo JR, Grimm AA, Imai S | title = The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells | journal = The Journal of Biological Chemistry | volume = 279 | issue = 49 | pages = 50754–63 | date = December 2004 | pmid = 15381699 | doi = 10.1074/jbc.M408388200 }}</ref> determined biochemically that the mouse PBEF gene product encodes a Nampt enzyme, capable of modulating intracellular NAD levels. Others have since confirmed these findings.<ref name="pmid15947248">{{cite journal | vauthors = van der Veer E, Nong Z, O'Neil C, Urquhart B, Freeman D, Pickering JG | title = Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation | journal = Circulation Research | volume = 97 | issue = 1 | pages = 25–34 | date = July 2005 | pmid = 15947248 | doi = 10.1161/01.RES.0000173298.38808.27 }}</ref> More recently, several groups have reported the crystal structure of Nampt/PBEF/visfatin and they all show that this protein is a dimeric type II phosphoribosyltransferase enzyme involved in NAD biosynthesis.<ref name="pmid16783373">{{cite journal | vauthors = Wang T, Zhang X, Bheda P, Revollo JR, Imai S, Wolberger C | title = Structure of Nampt/PBEF/visfatin, a mammalian NAD+ biosynthetic enzyme | journal = Nature Structural & Molecular Biology | volume = 13 | issue = 7 | pages = 661–2 | date = July 2006 | pmid = 16783373 | doi = 10.1038/nsmb1114 }}</ref><ref name="pmid16901503">{{cite journal | vauthors = Kim MK, Lee JH, Kim H, Park SJ, Kim SH, Kang GB, Lee YS, Kim JB, Kim KK, Suh SW, Eom SH | title = Crystal structure of visfatin/pre-B cell colony-enhancing factor 1/nicotinamide phosphoribosyltransferase, free and in complex with the anti-cancer agent FK-866 | journal = Journal of Molecular Biology | volume = 362 | issue = 1 | pages = 66–77 | date = September 2006 | pmid = 16901503 | doi = 10.1016/j.jmb.2006.06.082 }}</ref><ref name="pmid16783377">{{cite journal | vauthors = Khan JA, Tao X, Tong L | title = Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents | journal = Nature Structural & Molecular Biology | volume = 13 | issue = 7 | pages = 582–8 | date = July 2006 | pmid = 16783377 | doi = 10.1038/nsmb1105 }}</ref>


===Hormone claim retracted===
===Hormone claim retracted===
Although the original cytokine function of PBEF has not been confirmed to date, others have since reported or suggested a cytokine-like function for this protein.<ref name="pmid15124023">{{cite journal | vauthors = Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, Marshall JC | title = Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis | journal = J. Clin. Invest. | volume = 113 | issue = 9 | pages = 1318–27 |date=May 2004 | pmid = 15124023 | pmc = 398427 | doi = 10.1172/JCI19930 | url = | issn = }}</ref> In particular, Nampt/PBEF was recently re-identified as a “new visceral fat-derived hormone” named visfatin.<ref name="pmid15604363">{{cite journal | vauthors = Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I | title = Visfatin: a protein secreted by visceral fat that mimics the effects of insulin | journal = Science | volume = 307 | issue = 5708 | pages = 426–30 |date=January 2005 | pmid = 15604363 | doi = 10.1126/science.1097243 | url = | issn = }}{{Retracted paper|{{PMID|17962537}}|intentional=yes}}</ref> It is reported that visfatin is enriched in the visceral fat of both humans and mice and that its plasma levels increase during the development of obesity.<ref name="pmid15604363"/> Noteworthy is that visfatin is reported to exert insulin-mimetic effects in cultured cells and to lower plasma glucose levels in mice by binding to and activating the insulin receptor.<ref name="pmid15604363"/> However, the physiological relevance of visfatin is still in question because its plasma concentration is 40 to 100-fold lower than that of insulin despite having similar receptor-binding affinity.<ref name="pmid15604363"/><ref name="pmid16531748">{{cite journal | vauthors = Stephens JM, Vidal-Puig AJ | title = An update on visfatin/pre-B cell colony-enhancing factor, an ubiquitously expressed, illusive cytokine that is regulated in obesity | journal = Curr. Opin. Lipidol. | volume = 17 | issue = 2 | pages = 128–31 |date=April 2006 | pmid = 16531748 | doi = 10.1097/01.mol.0000217893.77746.4b | url = | issn = }}</ref><ref name="pmid16401830">{{cite journal | author = Arner P | title = Visfatin--a true or false trail to type 2 diabetes mellitus | journal = J. Clin. Endocrinol. Metab. | volume = 91 | issue = 1 | pages = 28–30 |date=January 2006 | pmid = 16401830 | doi = 10.1210/jc.2005-2391 | url = | issn = }}</ref> In addition, the ability of visfatin to bind and activate the insulin-receptor has yet to be confirmed by other groups.
Although the original cytokine function of PBEF has not been confirmed to date, others have since reported or suggested a cytokine-like function for this protein.<ref name="pmid15124023">{{cite journal | vauthors = Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, Marshall JC | title = Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis | journal = The Journal of Clinical Investigation | volume = 113 | issue = 9 | pages = 1318–27 | date = May 2004 | pmid = 15124023 | pmc = 398427 | doi = 10.1172/JCI19930 }}</ref> In particular, Nampt/PBEF was recently re-identified as a “new visceral fat-derived hormone” named visfatin.<ref name="pmid15604363">{{cite journal | vauthors = Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I | title = Visfatin: a protein secreted by visceral fat that mimics the effects of insulin | journal = Science | volume = 307 | issue = 5708 | pages = 426–30 | date = January 2005 | pmid = 15604363 | doi = 10.1126/science.1097243 }}{{Retracted paper|{{PMID|17962537}}|intentional=yes}}</ref> It is reported that visfatin is enriched in the visceral fat of both humans and mice and that its plasma levels increase during the development of obesity.<ref name="pmid15604363"/> Noteworthy is that visfatin is reported to exert insulin-mimetic effects in cultured cells and to lower plasma glucose levels in mice by binding to and activating the insulin receptor.<ref name="pmid15604363"/> However, the physiological relevance of visfatin is still in question because its plasma concentration is 40 to 100-fold lower than that of insulin despite having similar receptor-binding affinity.<ref name="pmid15604363"/><ref name="pmid16531748">{{cite journal | vauthors = Stephens JM, Vidal-Puig AJ | title = An update on visfatin/pre-B cell colony-enhancing factor, an ubiquitously expressed, illusive cytokine that is regulated in obesity | journal = Current Opinion in Lipidology | volume = 17 | issue = 2 | pages = 128–31 | date = April 2006 | pmid = 16531748 | doi = 10.1097/01.mol.0000217893.77746.4b }}</ref><ref name="pmid16401830">{{cite journal | vauthors = Arner P | title = Visfatin--a true or false trail to type 2 diabetes mellitus | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 91 | issue = 1 | pages = 28–30 | date = January 2006 | pmid = 16401830 | doi = 10.1210/jc.2005-2391 }}</ref> In addition, the ability of visfatin to bind and activate the insulin-receptor has yet to be confirmed by other groups.


On 26 October 2007, A. Fukuhara (first author), I.Shimomura (senior author) and the other co-authors of the paper,<ref name="pmid15604363"/> who first described Visfatin as a visceral-fat derived hormone that acts by binding and activating the [[insulin]] receptor, retracted the entire paper<ref name="pmid15604363"/> at the suggestion of the editor of the journal 'Science' and recommendation of the Faculty Council of Osaka University Medical School after a report of the Committee for Research Integrity.<ref name="pmid17962537">{{cite journal | vauthors = Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I | title = Retraction | journal = Science | volume = 318 | issue = 5850 | pages = 565 |date=October 2007 | pmid = 17962537 | doi = 10.1126/science.318.5850.565b | url = | issn = }}</ref>
On 26 October 2007, A. Fukuhara (first author), I.Shimomura (senior author) and the other co-authors of the paper,<ref name="pmid15604363"/> who first described Visfatin as a visceral-fat derived hormone that acts by binding and activating the [[insulin]] receptor, retracted the entire paper<ref name="pmid15604363"/> at the suggestion of the editor of the journal 'Science' and recommendation of the Faculty Council of Osaka University Medical School after a report of the Committee for Research Integrity.<ref name="pmid17962537">{{cite journal | vauthors = Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I | title = Retraction | journal = Science | volume = 318 | issue = 5850 | pages = 565 | date = October 2007 | pmid = 17962537 | doi = 10.1126/science.318.5850.565b }}</ref>


==As a drug target==
==As a drug target==
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[[cutaneous T-cell lymphoma]] (CTL), and refractory or relapsed B-chronic lymphocytic [[leukemia]].<!-- See [[TopoTarget]] -->
[[cutaneous T-cell lymphoma]] (CTL), and refractory or relapsed B-chronic lymphocytic [[leukemia]].<!-- See [[TopoTarget]] -->


[[Anti-aging]] biomedical company [[Calico (company)|Calico]] has licensed the experimental  [[P7C3]] analogs involved in enhancing NAMPT activity.<ref>{{cite web|title=UT Southwestern researchers discover novel class of NAMPT activators for neurodegenerative disease; Calico enters into exclusive collaboration with 2M to develop UTSW technology|url=http://www.prnewswire.com/news-releases/ut-southwestern-researchers-discover-novel-class-of-nampt-activators-for-neurodegenerative-disease-calico-enters-into-exclusive-collaboration-with-2m-to-develop-utsw-technology-274773691.html}}</ref> P7C3 compounds have been shown in a number of publications to be beneficial in animal models for age-related neurodegeneration.<ref>{{cite journal|title=NAMPT neuroprotection|doi=10.1038/scibx.2014.1112}}</ref><ref>{{cite journal|title=P7C3 Neuroprotective Chemicals Function by Activating the Rate-Limiting Enzyme in NAD Salvage|doi=10.1016/j.cell.2014.07.040}}</ref>
[[Anti-aging]] biomedical company [[Calico (company)|Calico]] has licensed the experimental  [[P7C3]] analogs involved in enhancing NAMPT activity.<ref>{{cite web|title=UT Southwestern researchers discover novel class of NAMPT activators for neurodegenerative disease; Calico enters into exclusive collaboration with 2M to develop UTSW technology|url=http://www.prnewswire.com/news-releases/ut-southwestern-researchers-discover-novel-class-of-nampt-activators-for-neurodegenerative-disease-calico-enters-into-exclusive-collaboration-with-2m-to-develop-utsw-technology-274773691.html}}</ref> P7C3 compounds have been shown in a number of publications to be beneficial in animal models for age-related neurodegeneration.<ref>{{cite journal|title=NAMPT neuroprotection|doi=10.1038/scibx.2014.1112}}</ref><ref>{{cite journal | vauthors = Wang G, Han T, Nijhawan D, Theodoropoulos P, Naidoo J, Yadavalli S, Mirzaei H, Pieper AA, Ready JM, McKnight SL | title = P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage | journal = Cell | volume = 158 | issue = 6 | pages = 1324–1334 | date = September 2014 | pmid = 25215490 | doi = 10.1016/j.cell.2014.07.040 }}</ref>


==References==
== References ==
{{Reflist}}
{{Reflist}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
* {{cite journal | vauthors = Preiss J, Handler P | last-author-amp = yes | year = 1957 | title = Enzymatic synthesis of nicotinamide mononucleotide | journal = J. Biol. Chem.  | volume = 225 | pages = 759&ndash;770 }}
* {{cite journal | vauthors = Preiss J, Handler P | last-author-amp = yes | year = 1957 | title = Enzymatic synthesis of nicotinamide mononucleotide | journal = J. Biol. Chem.  | volume = 225 | pages = 759&ndash;770 }}
* {{cite journal | vauthors=Stephens JM, Vidal-Puig AJ |title=An update on visfatin/pre-B cell colony-enhancing factor, an ubiquitously expressed, illusive cytokine that is regulated in obesity. |journal=Curr. Opin. Lipidol. |volume=17 |issue= 2 |pages= 128–31 |year= 2007 |pmid= 16531748 |doi= 10.1097/01.mol.0000217893.77746.4b }}
* {{cite journal | vauthors = Stephens JM, Vidal-Puig AJ | title = An update on visfatin/pre-B cell colony-enhancing factor, an ubiquitously expressed, illusive cytokine that is regulated in obesity | journal = Current Opinion in Lipidology | volume = 17 | issue = 2 | pages = 128–31 | date = April 2006 | pmid = 16531748 | doi = 10.1097/01.mol.0000217893.77746.4b }}
* {{cite journal | author=Bełtowski J |title=Apelin and visfatin: unique "beneficial" adipokines upregulated in obesity? |journal=Med. Sci. Monit. |volume=12 |issue= 6 |pages= RA112–9 |year= 2006 |pmid= 16733497 |doi=  }}
* {{cite journal | vauthors = Bełtowski J | title = Apelin and visfatin: unique "beneficial" adipokines upregulated in obesity? | journal = Medical Science Monitor | volume = 12 | issue = 6 | pages = RA112-9 | date = June 2006 | pmid = 16733497 | doi =  }}
* {{cite journal | vauthors=Pilz S, Mangge H, Obermayer-Pietsch B, März W |title=Visfatin/pre-B-cell colony-enhancing factor: a protein with various suggested functions. |journal=J. Endocrinol. Invest. |volume=30 |issue= 2 |pages= 138–44 |year= 2007 |pmid= 17392604 |doi= 10.1007/bf03347412}}
* {{cite journal | vauthors = Pilz S, Mangge H, Obermayer-Pietsch B, März W | title = Visfatin/pre-B-cell colony-enhancing factor: a protein with various suggested functions | journal = [[Journal of Endocrinological Investigation]] | volume = 30 | issue = 2 | pages = 138–44 | date = February 2007 | pmid = 17392604 | doi = 10.1007/bf03347412 }}
* {{cite journal | vauthors=Siderovski DP, Blum S, Forsdyke RE, Forsdyke DR |title=A set of human putative lymphocyte G0/G1 switch genes includes genes homologous to rodent cytokine and zinc finger protein-encoding genes. |journal=DNA Cell Biol. |volume=9 |issue= 8 |pages= 579–87 |year= 1991 |pmid= 1702972 |doi=10.1089/dna.1990.9.579 }}
* {{cite journal | vauthors = Siderovski DP, Blum S, Forsdyke RE, Forsdyke DR | title = A set of human putative lymphocyte G0/G1 switch genes includes genes homologous to rodent cytokine and zinc finger protein-encoding genes | journal = DNA and Cell Biology | volume = 9 | issue = 8 | pages = 579–87 | date = October 1990 | pmid = 1702972 | doi = 10.1089/dna.1990.9.579 }}
* {{cite journal  |title=Toward a complete human genome sequence. |journal=Genome Res. |volume=8 |issue= 11 |pages= 1097–108 |year= 1999 |pmid= 9847074 |doi= 10.1101/gr.8.11.1097}}
* {{cite journal | vauthors = | title = Toward a complete human genome sequence | journal = Genome Research | volume = 8 | issue = 11 | pages = 1097–108 | date = November 1998 | pmid = 9847074 | doi = 10.1101/gr.8.11.1097 }}
* {{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 }}
* {{cite journal | vauthors = Rongvaux A, Shea RJ, Mulks MH, Gigot D, Urbain J, Leo O, Andris F | title = Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis | journal = European Journal of Immunology | volume = 32 | issue = 11 | pages = 3225–34 | date = November 2002 | pmid = 12555668 | doi = 10.1002/1521-4141(200211)32:11<3225::AID-IMMU3225>3.0.CO;2-L }}
* {{cite journal  |vauthors=Rongvaux A, Shea RJ, Mulks MH, etal |title=Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis. |journal=Eur. J. Immunol. |volume=32 |issue= 11 |pages= 3225–34 |year= 2003 |pmid= 12555668 |doi= 10.1002/1521-4141(200211)32:11<3225::AID-IMMU3225>3.0.CO;2-L }}
* {{cite journal | vauthors = Kitani T, Okuno S, Fujisawa H | title = Growth phase-dependent changes in the subcellular localization of pre-B-cell colony-enhancing factor | journal = FEBS Letters | volume = 544 | issue = 1-3 | pages = 74–8 | date = June 2003 | pmid = 12782293 | doi = 10.1016/S0014-5793(03)00476-9 }}
* {{cite journal   |vauthors=Scherer SW, Cheung J, MacDonald JR, etal |title=Human chromosome 7: DNA sequence and biology. |journal=Science |volume=300 |issue= 5620 |pages= 767–72 |year= 2003 |pmid= 12690205  | pmc=2882961 |doi= 10.1126/science.1083423 }}
* {{cite journal | vauthors = Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA | title = Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport | journal = Experimental Cell Research | volume = 289 | issue = 2 | pages = 211–21 | date = October 2003 | pmid = 14499622 | doi = 10.1016/S0014-4827(03)00261-1 }}
* {{cite journal  | vauthors=Kitani T, Okuno S, Fujisawa H |title=Growth phase-dependent changes in the subcellular localization of pre-B-cell colony-enhancing factor. |journal=FEBS Lett. |volume=544 |issue= 1–3 |pages= 74–8 |year= 2003 |pmid= 12782293 |doi=10.1016/S0014-5793(03)00476-9 }}
* {{cite journal | vauthors = Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, Marshall JC | title = Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis | journal = The Journal of Clinical Investigation | volume = 113 | issue = 9 | pages = 1318–27 | date = May 2004 | pmid = 15124023 | pmc = 398427 | doi = 10.1172/JCI19930 }}
* {{cite journal   |vauthors=Hillier LW, Fulton RS, Fulton LA, etal |title=The DNA sequence of human chromosome 7 |journal=Nature |volume=424 |issue= 6945 |pages= 157–64 |year= 2003 |pmid= 12853948 |doi= 10.1038/nature01782 }}
* {{cite journal | vauthors = Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ | title = Immunoaffinity profiling of tyrosine phosphorylation in cancer cells | journal = Nature Biotechnology | volume = 23 | issue = 1 | pages = 94–101 | date = January 2005 | pmid = 15592455 | doi = 10.1038/nbt1046 }}
* {{cite journal  |vauthors=Reuter TY, Medhurst AL, Waisfisz Q, etal |title=Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport |journal=Exp. Cell Res. |volume=289 |issue= 2 |pages= 211–21 |year= 2003 |pmid= 14499622 |doi=10.1016/S0014-4827(03)00261-1 }}
* {{cite journal | vauthors = Janssen JJ, Klaver SM, Waisfisz Q, Pasterkamp G, de Kleijn DP, Schuurhuis GJ, Ossenkoppele GJ | title = Identification of genes potentially involved in disease transformation of CML | journal = Leukemia | volume = 19 | issue = 6 | pages = 998–1004 | date = June 2005 | pmid = 15815727 | doi = 10.1038/sj.leu.2403735 }}
* {{cite journal   |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
* {{cite journal | vauthors = van der Veer E, Nong Z, O'Neil C, Urquhart B, Freeman D, Pickering JG | title = Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation | journal = Circulation Research | volume = 97 | issue = 1 | pages = 25–34 | date = July 2005 | pmid = 15947248 | doi = 10.1161/01.RES.0000173298.38808.27 }}
* {{cite journal  |vauthors=Jia SH, Li Y, Parodo J, etal |title=Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis |journal=J. Clin. Invest. |volume=113 |issue= 9 |pages= 1318–27 |year= 2004 |pmid= 15124023 |doi= 10.1172/JCI19930  | pmc=398427 }}
* {{cite journal | vauthors = Ognjanovic S, Ku TL, Bryant-Greenwood GD | title = Pre-B-cell colony-enhancing factor is a secreted cytokine-like protein from the human amniotic epithelium | journal = American Journal of Obstetrics and Gynecology | volume = 193 | issue = 1 | pages = 273–82 | date = July 2005 | pmid = 16021090 | pmc = 1382169 | doi = 10.1016/j.ajog.2004.11.003 }}
* {{cite journal  |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928 }}
* {{cite journal   |vauthors=Rush J, Moritz A, Lee KA, etal |title=Immunoaffinity profiling of tyrosine phosphorylation in cancer cells |journal=Nat. Biotechnol. |volume=23 |issue= 1 |pages= 94–101 |year= 2005 |pmid= 15592455 |doi= 10.1038/nbt1046 }}
* {{cite journal   |vauthors=Janssen JJ, Klaver SM, Waisfisz Q, etal |title=Identification of genes potentially involved in disease transformation of CML |journal=Leukemia |volume=19 |issue= 6 |pages= 998–1004 |year= 2005 |pmid= 15815727 |doi= 10.1038/sj.leu.2403735 }}
* {{cite journal   |vauthors=van der Veer E, Nong Z, O'Neil C, etal |title=Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation |journal=Circ. Res. |volume=97 |issue= 1 |pages= 25–34 |year= 2005 |pmid= 15947248 |doi= 10.1161/01.RES.0000173298.38808.27 }}
* {{cite journal | vauthors=Ognjanovic S, Ku TL, Bryant-Greenwood GD |title=Pre-B-cell colony-enhancing factor is a secreted cytokine-like protein from the human amniotic epithelium |journal=Am. J. Obstet. Gynecol. |volume=193 |issue= 1 |pages= 273–82 |year= 2005 |pmid= 16021090 |doi= 10.1016/j.ajog.2004.11.003 | pmc=1382169 }}
}}
{{refend}}
{{refend}}


==External links==
== External links ==
* {{MeshName|visfatin,+human}}
* {{MeshName|visfatin,+human}}
* {{UCSC genome browser|NAMPT}}
* {{UCSC genome browser|NAMPT}}
* {{UCSC gene details|NAMPT}}
* {{UCSC gene details|NAMPT}}
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{{PDB Gallery|geneid=10135}}
{{PDB Gallery|geneid=10135}}

Revision as of 18:14, 4 December 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
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UniProt
RefSeq (mRNA)

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RefSeq (protein)

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nicotinamide phosphoribosyltransferase
Identifiers
EC number2.4.2.12
CAS number9030-27-7
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
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PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

Nicotinamide phosphoribosyltransferase (NAmPRTase or Nampt) also known as pre-B-cell colony-enhancing factor 1 (PBEF1) or visfatin is an enzyme that in humans is encoded by the NAMPT gene.[1] This protein is the rate-limiting enzyme in the Nicotinamide adenine dinucleotide (NAD+) salvage pathway that converts nicotinamide to nicotinamide mononucleotide in mammals to enable NAD+ biosynthesis.[2] NAMPT has also been reported to be a cytokine (PBEF) that promotes B cell maturation and inhibits neutrophil apoptosis.

Expression & Regulation

NAMPT is downregulated by an increase of miR-34a in obesity via a 3'UTR functional binding site of NAMPT mRNA resulting in a reduction of NAD(+) and decreased SIRT1 activity.[3]

Reaction

NAMPT catalyzes the following chemical reaction:

nicotinamide + 5-phosphoribosyl-1-pyrophosphate (PRPP) <math>\rightleftharpoons</math> nicotinamide mononucleotide (NMN) + pyrophosphate (PPi)

Thus, the two substrates of this enzyme are nicotinamide and 5-phosphoribosyl-1-pyrophosphate (PRRP), whereas its two products are nicotinamide mononucleotide and pyrophosphate.[2]

This enzyme belongs to the family of glycosyltransferases, to be specific, the pentosyltransferases. This enzyme participates in nicotinate and nicotinamide metabolism.

Function

NAmPRTase catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, one step in the biosynthesis of nicotinamide adenine dinucleotide. The protein is an adipokine that is localized to the bloodstream and has various functions, including the promotion of vascular smooth muscle cell maturation and inhibition of neutrophil apoptosis. It also activates insulin receptor and has insulin-mimetic effects, lowering blood glucose and improving insulin sensitivity. However, the paper was retracted in 2007. The protein is highly expressed in visceral fat and serum levels of the protein correlate with obesity. This gene has a pseudogene on chromosome 10.[4][5]

Recently, it has been demonstrated that NAMPT could bind to and activate TLR4. [6]

Nomenclature

The systematic name of this enzyme class is nicotinamide-nucleotide:diphosphate phospho-alpha-D-ribosyltransferase. Other names in common use include:

  • NMN pyrophosphorylase,
  • nicotinamide mononucleotide pyrophosphorylase,
  • nicotinamide mononucleotide synthetase, and
  • NMN synthetase.

History

Nampt/PBEF/visfatin was originally cloned as a putative cytokine shown to enhance the maturation of B cell precursors in the presence of Interleukin-7 (IL-7) and stem cell factor, it was therefore named “pre-B cell colony-enhancing factor” (PBEF).[1] When the gene encoding the bacterial nicotinamide phosphoribosyltransferase (nadV) was first isolated in Haemophilus ducreyi, it was found to exhibit significant homology to the mammalian PBEF gene.[7] Rongvaux et al.[8] demonstrated genetically that the mouse PBEF gene conferred Nampt enzymatic activity and NAD-independent growth to bacteria lacking nadV. Revollo et al.[9] determined biochemically that the mouse PBEF gene product encodes a Nampt enzyme, capable of modulating intracellular NAD levels. Others have since confirmed these findings.[10] More recently, several groups have reported the crystal structure of Nampt/PBEF/visfatin and they all show that this protein is a dimeric type II phosphoribosyltransferase enzyme involved in NAD biosynthesis.[11][12][13]

Hormone claim retracted

Although the original cytokine function of PBEF has not been confirmed to date, others have since reported or suggested a cytokine-like function for this protein.[14] In particular, Nampt/PBEF was recently re-identified as a “new visceral fat-derived hormone” named visfatin.[15] It is reported that visfatin is enriched in the visceral fat of both humans and mice and that its plasma levels increase during the development of obesity.[15] Noteworthy is that visfatin is reported to exert insulin-mimetic effects in cultured cells and to lower plasma glucose levels in mice by binding to and activating the insulin receptor.[15] However, the physiological relevance of visfatin is still in question because its plasma concentration is 40 to 100-fold lower than that of insulin despite having similar receptor-binding affinity.[15][16][17] In addition, the ability of visfatin to bind and activate the insulin-receptor has yet to be confirmed by other groups.

On 26 October 2007, A. Fukuhara (first author), I.Shimomura (senior author) and the other co-authors of the paper,[15] who first described Visfatin as a visceral-fat derived hormone that acts by binding and activating the insulin receptor, retracted the entire paper[15] at the suggestion of the editor of the journal 'Science' and recommendation of the Faculty Council of Osaka University Medical School after a report of the Committee for Research Integrity.[18]

As a drug target

APO866 is an experimental drug that inhibits this enzyme.[19] It is being tested for treatment of advanced melanoma, cutaneous T-cell lymphoma (CTL), and refractory or relapsed B-chronic lymphocytic leukemia.

Anti-aging biomedical company Calico has licensed the experimental P7C3 analogs involved in enhancing NAMPT activity.[20] P7C3 compounds have been shown in a number of publications to be beneficial in animal models for age-related neurodegeneration.[21][22]

References

  1. 1.0 1.1 Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I (February 1994). "Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor". Molecular and Cellular Biology. 14 (2): 1431–7. PMC 358498. PMID 8289818.
  2. 2.0 2.1 Revollo JR, Grimm AA, Imai S (March 2007). "The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/visfatin in mammals". Current Opinion in Gastroenterology. 23 (2): 164–70. doi:10.1097/MOG.0b013e32801b3c8f. PMID 17268245.
  3. Choi SE, Fu T, Seok S, Kim DH, Yu E, Lee KW, Kang Y, Li X, Kemper B, Kemper JK (December 2013). "Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT". Aging Cell. 12 (6): 1062–72. doi:10.1111/acel.12135. PMID 23834033.
  4. "Entrez Gene: PBEF1 pre-B-cell colony enhancing factor 1".
  5. Fukuhara, Atsunori; Matsuda, Morihiro; Nishizawa, Masako; Segawa, Katsumori; Tanaka, Masaki; Kishimoto, Kae; Matsuki, Yasushi; Murakami, Mirei; Ichisaka, Tomoko (2007-10-26). "Retraction". Science (New York, N.Y.). 318 (5850): 565. doi:10.1126/science.318.5850.565b. ISSN 1095-9203. PMID 17962537.
  6. Garcia, Joe G. N.; Liang, Jie; Wang, Ting; Yousef, Mohammed; Saadat, Laleh; Letsiou, Eleftheria; Sammani, Saad; Quijada, Hector; Siddiqui, Shahid S. (2015-08-14). "Unique Toll-Like Receptor 4 Activation by NAMPT/PBEF Induces NFκB Signaling and Inflammatory Lung Injury". Scientific Reports. 5: 13135. doi:10.1038/srep13135. ISSN 2045-2322.
  7. Martin PR, Shea RJ, Mulks MH (February 2001). "Identification of a plasmid-encoded gene from Haemophilus ducreyi which confers NAD independence". Journal of Bacteriology. 183 (4): 1168–74. doi:10.1128/JB.183.4.1168-1174.2001. PMC 94989. PMID 11157928.
  8. Rongvaux A, Shea RJ, Mulks MH, Gigot D, Urbain J, Leo O, Andris F (November 2002). "Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis". European Journal of Immunology. 32 (11): 3225–34. doi:10.1002/1521-4141(200211)32:11<3225::AID-IMMU3225>3.0.CO;2-L. PMID 12555668.
  9. Revollo JR, Grimm AA, Imai S (December 2004). "The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells". The Journal of Biological Chemistry. 279 (49): 50754–63. doi:10.1074/jbc.M408388200. PMID 15381699.
  10. van der Veer E, Nong Z, O'Neil C, Urquhart B, Freeman D, Pickering JG (July 2005). "Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation". Circulation Research. 97 (1): 25–34. doi:10.1161/01.RES.0000173298.38808.27. PMID 15947248.
  11. Wang T, Zhang X, Bheda P, Revollo JR, Imai S, Wolberger C (July 2006). "Structure of Nampt/PBEF/visfatin, a mammalian NAD+ biosynthetic enzyme". Nature Structural & Molecular Biology. 13 (7): 661–2. doi:10.1038/nsmb1114. PMID 16783373.
  12. Kim MK, Lee JH, Kim H, Park SJ, Kim SH, Kang GB, Lee YS, Kim JB, Kim KK, Suh SW, Eom SH (September 2006). "Crystal structure of visfatin/pre-B cell colony-enhancing factor 1/nicotinamide phosphoribosyltransferase, free and in complex with the anti-cancer agent FK-866". Journal of Molecular Biology. 362 (1): 66–77. doi:10.1016/j.jmb.2006.06.082. PMID 16901503.
  13. Khan JA, Tao X, Tong L (July 2006). "Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents". Nature Structural & Molecular Biology. 13 (7): 582–8. doi:10.1038/nsmb1105. PMID 16783377.
  14. Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, Marshall JC (May 2004). "Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis". The Journal of Clinical Investigation. 113 (9): 1318–27. doi:10.1172/JCI19930. PMC 398427. PMID 15124023.
  15. 15.0 15.1 15.2 15.3 15.4 15.5 Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I (January 2005). "Visfatin: a protein secreted by visceral fat that mimics the effects of insulin". Science. 307 (5708): 426–30. doi:10.1126/science.1097243. PMID 15604363. (Retracted, see PMID 17962537)
  16. Stephens JM, Vidal-Puig AJ (April 2006). "An update on visfatin/pre-B cell colony-enhancing factor, an ubiquitously expressed, illusive cytokine that is regulated in obesity". Current Opinion in Lipidology. 17 (2): 128–31. doi:10.1097/01.mol.0000217893.77746.4b. PMID 16531748.
  17. Arner P (January 2006). "Visfatin--a true or false trail to type 2 diabetes mellitus". The Journal of Clinical Endocrinology and Metabolism. 91 (1): 28–30. doi:10.1210/jc.2005-2391. PMID 16401830.
  18. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I (October 2007). "Retraction". Science. 318 (5850): 565. doi:10.1126/science.318.5850.565b. PMID 17962537.
  19. APO866 Not Effective for Cutaneous T-Cell Lymphoma. March 2016
  20. "UT Southwestern researchers discover novel class of NAMPT activators for neurodegenerative disease; Calico enters into exclusive collaboration with 2M to develop UTSW technology".
  21. "NAMPT neuroprotection". doi:10.1038/scibx.2014.1112.
  22. Wang G, Han T, Nijhawan D, Theodoropoulos P, Naidoo J, Yadavalli S, Mirzaei H, Pieper AA, Ready JM, McKnight SL (September 2014). "P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage". Cell. 158 (6): 1324–1334. doi:10.1016/j.cell.2014.07.040. PMID 25215490.

Further reading

External links