Dipeptidyl peptidase-4: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (→‎Clinical significance: task, replaced: Current Opinion in Endocrinology, Diabetes, and Obesity → Current Opinion in Endocrinology, Diabetes and Obesity using AWB)
 
imported>Boghog
(consistent citation formatting)
Line 1: Line 1:
{{Infobox_gene}}
{{Infobox_gene}}


'''Dipeptidyl peptidase-4''' ('''DPP4'''), also known as '''adenosine deaminase complexing protein 2''' or '''CD26''' ([[cluster of differentiation]] 26) is a [[protein]] that, in humans, is encoded by the ''DPP4'' [[gene]].<ref name="pmid8101391">{{cite journal | vauthors = Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C | title = Direct association of adenosine deaminase with a T cell activation antigen, CD26 | journal = Science | volume = 261 | issue = 5120 | pages = 466–9 | date = Jul 1993 | pmid = 8101391 | doi = 10.1126/science.8101391 }}</ref> DPP4 is related to [[ATRN|attractin]], [[FAP (gene)|FAP]], [[DPP8]] and [[DPP9]].
'''Dipeptidyl peptidase-4''' ('''DPP4'''), also known as '''adenosine deaminase complexing protein 2''' or '''CD26''' ([[cluster of differentiation]] 26) is a [[protein]] that, in humans, is encoded by the ''DPP4'' [[gene]].<ref name="pmid8101391">{{cite journal | vauthors = Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C | title = Direct association of adenosine deaminase with a T cell activation antigen, CD26 | journal = Science | volume = 261 | issue = 5120 | pages = 466–9 | date = July 1993 | pmid = 8101391 | doi = 10.1126/science.8101391 }}</ref> DPP4 is related to [[FAP (gene)|FAP]], [[DPP8]], and [[DPP9]]. The enzyme was discovered in 1966 by Hopsu-Havu and Glenner<ref>{{cite journal | vauthors = Hopsu-Havu VK, Glenner GG | title = A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-beta-naphthylamide | journal = Histochemie. Histochemistry. Histochimie | volume = 7 | issue = 3 | pages = 197–201 | date = 1966 | pmid = 5959122 }}</ref>, and as a result of various studies on chemism, was called dipeptidyl peptidase IV [DP IV].


== Function ==
== Function ==
The protein encoded by the ''DPP4'' gene is an [[antigen]]ic [[enzyme]] expressed on the surface of most cell types and is associated with immune regulation, [[signal transduction]] and [[apoptosis]]. It is an intrinsic membrane [[glycoprotein]] and a [[serine]] [[exopeptidase]] that cleaves X-proline [[dipeptide]]s from the [[N-terminus]] of [[polypeptide]]s.
The protein encoded by the ''DPP4'' gene is an [[enzyme]] expressed on the surface of most cell types and is associated with immune regulation, [[signal transduction]], and [[apoptosis]]. It is a type II transmembrane [[glycoprotein]], but a soluble form, which lacks the intracellular and transmembrane part, is present in blood plasma and various body fluids. DPP-4 is a [[serine]] [[exopeptidase]] that cleaves X-proline or X-alanine [[dipeptide]]s from the [[N-terminus]] of [[polypeptide]]s. Peptide bonds involving the cyclic amino acid proline cannot be cleaved by the majority of proteases and an N-terminal X-proline "shields" various biopeptides.<ref>{{cite journal | vauthors = Vanhoof G, Goossens F, De Meester I, Hendriks D, Scharpé S | title = Proline motifs in peptides and their biological processing | journal = FASEB Journal | volume = 9 | issue = 9 | pages = 736–44 | date = June 1995 | pmid = 7601338 }}</ref> Extracellular proline-specific proteases therefore play an important role in the regulation of these biopeptides.  


It is a rather indiscriminate enzyme for which a diverse range of [[Substrate (biochemistry)|substrates]] are known.<ref name="pmid16700505">{{cite journal | vauthors = Chen X | title = Biochemical properties of recombinant prolyl dipeptidases DPP-IV and DPP8 | journal = Advances in Experimental Medicine and Biology | volume = 575 | issue =  | pages = 27–32 | year = 2006 | pmid = 16700505 | doi = 10.1007/0-387-32824-6_3 | isbn = 978-0-387-29058-4 | series = Advances in Experimental Medicine and Biology }}</ref> The substrates of CD26/DPPIV are [[proline]](or [[alanine]])-containing [[peptide]]s and include [[growth factor]]s, [[chemokine]]s, [[neuropeptide]]s, and [[vasoactive]] peptides. DPP4 plays a major role in [[glucose]] metabolism. It is responsible for the degradation of [[incretin]]s such as [[glucagon-like peptide-1|GLP-1]].<ref name="pmid17073841">{{cite journal | vauthors = Barnett A | title = DPP-4 inhibitors and their potential role in the management of type 2 diabetes | journal = International Journal of Clinical Practice | volume = 60 | issue = 11 | pages = 1454–70 | date = Nov 2006 | pmid = 17073841 | doi = 10.1111/j.1742-1241.2006.01178.x }}</ref> Furthermore, it appears to work as a suppressor in the development of [[cancer]] and [[tumours]].<ref>{{cite journal | vauthors = Pro B, Dang NH | title = CD26/dipeptidyl peptidase IV and its role in cancer | journal = Histology and Histopathology | volume = 19 | issue = 4 | pages = 1345–51 | date = Oct 2004 | pmid = 15375776 }}</ref><ref>{{cite journal | vauthors = Masur K, Schwartz F, Entschladen F, Niggemann B, Zaenker KS | title = DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells | journal = Regulatory Peptides | volume = 137 | issue = 3 | pages = 147–55 | date = Dec 2006 | pmid = 16908079 | doi = 10.1016/j.regpep.2006.07.003 }}</ref><ref>{{cite journal | vauthors = Wesley UV, McGroarty M, Homoyouni A | title = Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway | journal = Cancer Research | volume = 65 | issue = 4 | pages = 1325–34 | date = Feb 2005 | pmid = 15735018 | doi = 10.1158/0008-5472.CAN-04-1852 }}</ref>
DPP-4 is known to cleave a broad range of [[Substrate (biochemistry)|substrates]] including [[growth factor]]s, [[chemokine]]s, [[neuropeptide]]s, and [[vasoactive]] peptides.<ref name=":0">{{cite journal | vauthors = Mentlein R | title = Dipeptidyl-peptidase IV (CD26)--role in the inactivation of regulatory peptides | journal = Regulatory Peptides | volume = 85 | issue = 1 | pages = 9–24 | date = November 1999 | pmid = 10588446 }}</ref><ref>{{Cite journal|last=Busek|first=Petr|last2=Sedo|first2=Aleksi|date=2013-02-27|title=Dipeptidyl Peptidase-IV and Related Proteases in Brain Tumors|url=https://www.intechopen.com/books/evolution-of-the-molecular-biology-of-brain-tumors-and-the-therapeutic-implications/dipeptidyl-peptidase-iv-and-related-proteases-in-brain-tumors|journal=Evolution of the Molecular Biology of Brain Tumors and the Therapeutic Implications|language=en|volume=|pages=|doi=10.5772/53888|via=}}</ref><ref name="pmid16700505">{{cite journal | vauthors = Chen X | title = Biochemical properties of recombinant prolyl dipeptidases DPP-IV and DPP8 | journal = Advances in Experimental Medicine and Biology | volume = 575 | issue =  | pages = 27–32 | year = 2006 | pmid = 16700505 | doi = 10.1007/0-387-32824-6_3 | isbn = 978-0-387-29058-4 | series = Advances in Experimental Medicine and Biology }}</ref> The cleaved substrates loose their biological activity in the majority of cases, but in the case of the chemokine RANTES and neuropeptide Y, DPP-4 mediated cleavage leads to a shift in the receptor subtype binding.<ref name=":0" />
 
DPP4 plays a major role in [[glucose]] metabolism. It is responsible for the degradation of [[incretin]]s such as [[glucagon-like peptide-1|GLP-1]].<ref name="pmid17073841">{{cite journal | vauthors = Barnett A | title = DPP-4 inhibitors and their potential role in the management of type 2 diabetes | journal = International Journal of Clinical Practice | volume = 60 | issue = 11 | pages = 1454–70 | date = November 2006 | pmid = 17073841 | doi = 10.1111/j.1742-1241.2006.01178.x }}</ref> Furthermore, it appears to work as a suppressor in the development of some [[tumors]].<ref>{{cite journal | vauthors = Pro B, Dang NH | title = CD26/dipeptidyl peptidase IV and its role in cancer | journal = Histology and Histopathology | volume = 19 | issue = 4 | pages = 1345–51 | date = October 2004 | pmid = 15375776 | doi = 10.14670/HH-19.1345 }}</ref><ref>{{cite journal | vauthors = Masur K, Schwartz F, Entschladen F, Niggemann B, Zaenker KS | title = DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells | journal = Regulatory Peptides | volume = 137 | issue = 3 | pages = 147–55 | date = December 2006 | pmid = 16908079 | doi = 10.1016/j.regpep.2006.07.003 }}</ref><ref>{{cite journal | vauthors = Wesley UV, McGroarty M, Homoyouni A | title = Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway | journal = Cancer Research | volume = 65 | issue = 4 | pages = 1325–34 | date = February 2005 | pmid = 15735018 | doi = 10.1158/0008-5472.CAN-04-1852 }}</ref><ref>{{cite journal | vauthors = Busek P, Malík R, Sedo A | title = Dipeptidyl peptidase IV activity and/or structure homologues (DASH) and their substrates in cancer | journal = The International Journal of Biochemistry & Cell Biology | volume = 36 | issue = 3 | pages = 408–21 | date = March 2004 | pmid = 14687920 }}</ref>


DPP-4 also binds the enzyme [[adenosine deaminase]] specifically and with high affinity. The significance of this interaction has yet to be established.
DPP-4 also binds the enzyme [[adenosine deaminase]] specifically and with high affinity. The significance of this interaction has yet to be established.
Line 12: Line 14:
== Animal studies ==
== Animal studies ==


Animal studies suggest its pathogenetic role in development of [[fibrosis]] of various organs, such as liver and kidney.<ref name="pmid23475323">{{cite journal | vauthors = Kaji K, Yoshiji H, Ikenaka Y, Noguchi R, Aihara Y, Douhara A, Moriya K, Kawaratani H, Shirai Y, Yoshii J, Yanase K, Kitade M, Namisaki T, Fukui H | title = Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats | journal = Journal of Gastroenterology | volume = 49 | issue = 3 | pages = 481–91 | date = Mar 2014 | pmid = 23475323 | doi = 10.1007/s00535-013-0783-4 }}</ref><ref name="pmid24687121">{{cite journal | vauthors = Min HS, Kim JE, Lee MH, Song HK, Kang YS, Lee MJ, Lee JE, Kim HW, Cha JJ, Chung YY, Hyun YY, Han JY, Cha DR | title = Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction | journal = Laboratory Investigation | volume = 94 | issue = 6 | pages = 598–607 | date = Jun 2014 | pmid = 24687121 | doi = 10.1038/labinvest.2014.50 }}</ref>
Animal studies suggest its pathogenetic role in development of [[fibrosis]] of various organs, such as liver and kidney.<ref name="pmid23475323">{{cite journal | vauthors = Kaji K, Yoshiji H, Ikenaka Y, Noguchi R, Aihara Y, Douhara A, Moriya K, Kawaratani H, Shirai Y, Yoshii J, Yanase K, Kitade M, Namisaki T, Fukui H | title = Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats | journal = Journal of Gastroenterology | volume = 49 | issue = 3 | pages = 481–91 | date = March 2014 | pmid = 23475323 | doi = 10.1007/s00535-013-0783-4 }}</ref><ref name="pmid24687121">{{cite journal | vauthors = Min HS, Kim JE, Lee MH, Song HK, Kang YS, Lee MJ, Lee JE, Kim HW, Cha JJ, Chung YY, Hyun YY, Han JY, Cha DR | title = Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction | journal = Laboratory Investigation; A Journal of Technical Methods and Pathology | volume = 94 | issue = 6 | pages = 598–607 | date = June 2014 | pmid = 24687121 | doi = 10.1038/labinvest.2014.50 }}</ref>


== Clinical significance ==
== Clinical significance ==


CD26/DPPIV plays an important role in tumor biology, and is useful as a marker for various cancers, with its levels either on the cell surface or in the serum increased in some [[neoplasm]]s and decreased in others.<ref name="pmid17981655">{{cite journal | vauthors = Havre PA, Abe M, Urasaki Y, Ohnuma K, Morimoto C, Dang NH | title = The role of CD26/dipeptidyl peptidase IV in cancer | journal = Frontiers in Bioscience | volume = 13 | issue = 13 | pages = 1634–45 | year = 2008 | pmid = 17981655 | doi = 10.2741/2787 | url = http://www.bioscience.org/2008/v13/af/2787/fulltext.htm }}</ref>
CD26/DPPIV plays an important role in tumor biology, and is useful as a marker for various cancers, with its levels either on the cell surface or in the serum increased in some [[neoplasm]]s and decreased in others.<ref name="pmid17981655">{{cite journal | vauthors = Havre PA, Abe M, Urasaki Y, Ohnuma K, Morimoto C, Dang NH | title = The role of CD26/dipeptidyl peptidase IV in cancer | journal = Frontiers in Bioscience | volume = 13 | issue = 13 | pages = 1634–45 | date = January 2008 | pmid = 17981655 | doi = 10.2741/2787 | url = http://www.bioscience.org/2008/v13/af/2787/fulltext.htm }}</ref>


A new class of [[oral hypoglycemics]] called [[dipeptidyl peptidase-4 inhibitors]] work by inhibiting the action of this enzyme, thereby prolonging incretin effect in vivo.<ref name="pmid17940427">{{cite journal | vauthors = Rosenstock J, Zinman B | title = Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus | journal = Current Opinion in Endocrinology, Diabetes and Obesity | volume = 14 | issue = 2 | pages = 98–107 | date = Apr 2007 | pmid = 17940427 | doi = 10.1097/MED.0b013e3280a02f65 }}</ref>
A class of [[oral hypoglycemics]] called [[dipeptidyl peptidase-4 inhibitors]] works by inhibiting the action of this enzyme, thereby prolonging incretin effect ''in vivo''.<ref name="pmid17940427">{{cite journal | vauthors = Rosenstock J, Zinman B | title = Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus | journal = Current Opinion in Endocrinology, Diabetes, and Obesity | volume = 14 | issue = 2 | pages = 98–107 | date = April 2007 | pmid = 17940427 | doi = 10.1097/MED.0b013e3280a02f65 }}</ref>


A new [[coronavirus]] related to [[SARS coronavirus|SARS]], named [[Middle East respiratory syndrome coronavirus]], has been found to bind to DPP4.  DPP4 is found on the surface of cells in the airways (such as the lungs) and kidneys. Scientists may be able to use this to their advantage by blocking the virus's entry into the cell.<ref name="pmid23486063">{{cite journal | vauthors = Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL | title = Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC | journal = Nature | volume = 495 | issue = 7440 | pages = 251–4 | date = Mar 2013 | pmid = 23486063 | doi = 10.1038/nature12005 | laysummary = http://www.sciencenews.org/view/generic/id/348950/description/News_in_Brief_New_virus_uses_protein_handle_to_infect_cells | laysource = ScienceNews | publisher = ScienceNews }}</ref>
[[Middle East respiratory syndrome coronavirus]] has been found to bind to DPP4.  It is found on the surface of cells in the airways (such as the lungs) and kidneys. Scientists may be able to use this to their advantage by blocking the virus's entry into the cell.<ref name="pmid23486063">{{cite journal | vauthors = Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL | title = Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC | journal = Nature | volume = 495 | issue = 7440 | pages = 251–4 | date = March 2013 | pmid = 23486063 | doi = 10.1038/nature12005 | laysummary = http://www.sciencenews.org/view/generic/id/348950/description/News_in_Brief_New_virus_uses_protein_handle_to_infect_cells | laysource = ScienceNews | publisher = ScienceNews }}</ref>


== See also ==
== See also ==
Line 33: Line 35:
* {{cite journal | vauthors = Ansorge S, Bühling F, Kähne T, Lendeckel U, Reinhold D, Täger M, Wrenger S | title = CD26/dipeptidyl peptidase IV in lymphocyte growth regulation | journal = Advances in Experimental Medicine and Biology | volume = 421 | issue =  | pages = 127–40 | year = 1997 | pmid = 9330689 | doi = 10.1007/978-1-4757-9613-1_17 }}
* {{cite journal | vauthors = Ansorge S, Bühling F, Kähne T, Lendeckel U, Reinhold D, Täger M, Wrenger S | title = CD26/dipeptidyl peptidase IV in lymphocyte growth regulation | journal = Advances in Experimental Medicine and Biology | volume = 421 | issue =  | pages = 127–40 | year = 1997 | pmid = 9330689 | doi = 10.1007/978-1-4757-9613-1_17 }}
* {{cite journal | vauthors = Reinhold D, Kähne T, Steinbrecher A, Wrenger S, Neubert K, Ansorge S, Brocke S | title = The role of dipeptidyl peptidase IV (DP IV) enzymatic activity in T cell activation and autoimmunity | journal = Biological Chemistry | volume = 383 | issue = 7-8 | pages = 1133–8 | year = 2003 | pmid = 12437097 | doi = 10.1515/BC.2002.123 }}
* {{cite journal | vauthors = Reinhold D, Kähne T, Steinbrecher A, Wrenger S, Neubert K, Ansorge S, Brocke S | title = The role of dipeptidyl peptidase IV (DP IV) enzymatic activity in T cell activation and autoimmunity | journal = Biological Chemistry | volume = 383 | issue = 7-8 | pages = 1133–8 | year = 2003 | pmid = 12437097 | doi = 10.1515/BC.2002.123 }}
* {{cite journal | vauthors = Sato K, Dang NH | title = CD26: a novel treatment target for T-cell lymphoid malignancies? (Review) | journal = International Journal of Oncology | volume = 22 | issue = 3 | pages = 481–97 | date = Mar 2003 | pmid = 12579300 | doi = }}
* {{cite journal | vauthors = Sato K, Dang NH | title = CD26: a novel treatment target for T-cell lymphoid malignancies? (Review) | journal = International Journal of Oncology | volume = 22 | issue = 3 | pages = 481–97 | date = March 2003 | pmid = 12579300 | doi = 10.3892/ijo.22.3.481 }}
* {{cite journal | vauthors = de Meester I, Lambeir AM, Proost P, Scharpé S | title = Dipeptidyl peptidase IV substrates. An update on in vitro peptide hydrolysis by human DPPIV | journal = Advances in Experimental Medicine and Biology | volume = 524 | issue =  | pages = 3–17 | year = 2003 | pmid = 12675218 | doi = 10.1007/0-306-47920-6_1 | isbn = 0-306-47717-3 | series = Advances in Experimental Medicine and Biology }}
* {{cite journal | vauthors = de Meester I, Lambeir AM, Proost P, Scharpé S | title = Dipeptidyl peptidase IV substrates. An update on in vitro peptide hydrolysis by human DPPIV | journal = Advances in Experimental Medicine and Biology | volume = 524 | issue =  | pages = 3–17 | year = 2003 | pmid = 12675218 | doi = 10.1007/0-306-47920-6_1 | isbn = 0-306-47717-3 | series = Advances in Experimental Medicine and Biology }}
* {{cite journal | vauthors = Koch S, Anthonsen D, Skovbjerg H, Sjöström H | title = On the role of dipeptidyl peptidase IV in the digestion of an immunodominant epitope in celiac disease | journal = Advances in Experimental Medicine and Biology | volume = 524 | issue =  | pages = 181–7 | year = 2003 | pmid = 12675238 | doi = 10.1007/0-306-47920-6_22 | isbn = 0-306-47717-3 | series = Advances in Experimental Medicine and Biology }}
* {{cite journal | vauthors = Koch S, Anthonsen D, Skovbjerg H, Sjöström H | title = On the role of dipeptidyl peptidase IV in the digestion of an immunodominant epitope in celiac disease | journal = Advances in Experimental Medicine and Biology | volume = 524 | issue =  | pages = 181–7 | year = 2003 | pmid = 12675238 | doi = 10.1007/0-306-47920-6_22 | isbn = 0-306-47717-3 | series = Advances in Experimental Medicine and Biology }}
* {{cite journal | vauthors = Pro B, Dang NH | title = CD26/dipeptidyl peptidase IV and its role in cancer | journal = Histology and Histopathology | volume = 19 | issue = 4 | pages = 1345–51 | date = Oct 2004 | pmid = 15375776 | doi = }}
* {{cite journal | vauthors = Pro B, Dang NH | title = CD26/dipeptidyl peptidase IV and its role in cancer | journal = Histology and Histopathology | volume = 19 | issue = 4 | pages = 1345–51 | date = October 2004 | pmid = 15375776 | doi = 10.14670/HH-19.1345 }}
{{refend}}
{{refend}}


Revision as of 15:30, 29 December 2018

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

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Dipeptidyl peptidase-4 (DPP4), also known as adenosine deaminase complexing protein 2 or CD26 (cluster of differentiation 26) is a protein that, in humans, is encoded by the DPP4 gene.[1] DPP4 is related to FAP, DPP8, and DPP9. The enzyme was discovered in 1966 by Hopsu-Havu and Glenner[2], and as a result of various studies on chemism, was called dipeptidyl peptidase IV [DP IV].

Function

The protein encoded by the DPP4 gene is an enzyme expressed on the surface of most cell types and is associated with immune regulation, signal transduction, and apoptosis. It is a type II transmembrane glycoprotein, but a soluble form, which lacks the intracellular and transmembrane part, is present in blood plasma and various body fluids. DPP-4 is a serine exopeptidase that cleaves X-proline or X-alanine dipeptides from the N-terminus of polypeptides. Peptide bonds involving the cyclic amino acid proline cannot be cleaved by the majority of proteases and an N-terminal X-proline "shields" various biopeptides.[3] Extracellular proline-specific proteases therefore play an important role in the regulation of these biopeptides.

DPP-4 is known to cleave a broad range of substrates including growth factors, chemokines, neuropeptides, and vasoactive peptides.[4][5][6] The cleaved substrates loose their biological activity in the majority of cases, but in the case of the chemokine RANTES and neuropeptide Y, DPP-4 mediated cleavage leads to a shift in the receptor subtype binding.[4]

DPP4 plays a major role in glucose metabolism. It is responsible for the degradation of incretins such as GLP-1.[7] Furthermore, it appears to work as a suppressor in the development of some tumors.[8][9][10][11]

DPP-4 also binds the enzyme adenosine deaminase specifically and with high affinity. The significance of this interaction has yet to be established.

Animal studies

Animal studies suggest its pathogenetic role in development of fibrosis of various organs, such as liver and kidney.[12][13]

Clinical significance

CD26/DPPIV plays an important role in tumor biology, and is useful as a marker for various cancers, with its levels either on the cell surface or in the serum increased in some neoplasms and decreased in others.[14]

A class of oral hypoglycemics called dipeptidyl peptidase-4 inhibitors works by inhibiting the action of this enzyme, thereby prolonging incretin effect in vivo.[15]

Middle East respiratory syndrome coronavirus has been found to bind to DPP4. It is found on the surface of cells in the airways (such as the lungs) and kidneys. Scientists may be able to use this to their advantage by blocking the virus's entry into the cell.[16]

See also

References

  1. ↑ Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C (July 1993). "Direct association of adenosine deaminase with a T cell activation antigen, CD26". Science. 261 (5120): 466–9. doi:10.1126/science.8101391. PMID 8101391.
  2. ↑ Hopsu-Havu VK, Glenner GG (1966). "A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-beta-naphthylamide". Histochemie. Histochemistry. Histochimie. 7 (3): 197–201. PMID 5959122.
  3. ↑ Vanhoof G, Goossens F, De Meester I, Hendriks D, Scharpé S (June 1995). "Proline motifs in peptides and their biological processing". FASEB Journal. 9 (9): 736–44. PMID 7601338.
  4. ↑ 4.0 4.1 Mentlein R (November 1999). "Dipeptidyl-peptidase IV (CD26)--role in the inactivation of regulatory peptides". Regulatory Peptides. 85 (1): 9–24. PMID 10588446.
  5. ↑ Busek, Petr; Sedo, Aleksi (2013-02-27). "Dipeptidyl Peptidase-IV and Related Proteases in Brain Tumors". Evolution of the Molecular Biology of Brain Tumors and the Therapeutic Implications. doi:10.5772/53888.
  6. ↑ Chen X (2006). "Biochemical properties of recombinant prolyl dipeptidases DPP-IV and DPP8". Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology. 575: 27–32. doi:10.1007/0-387-32824-6_3. ISBN 978-0-387-29058-4. PMID 16700505.
  7. ↑ Barnett A (November 2006). "DPP-4 inhibitors and their potential role in the management of type 2 diabetes". International Journal of Clinical Practice. 60 (11): 1454–70. doi:10.1111/j.1742-1241.2006.01178.x. PMID 17073841.
  8. ↑ Pro B, Dang NH (October 2004). "CD26/dipeptidyl peptidase IV and its role in cancer". Histology and Histopathology. 19 (4): 1345–51. doi:10.14670/HH-19.1345. PMID 15375776.
  9. ↑ Masur K, Schwartz F, Entschladen F, Niggemann B, Zaenker KS (December 2006). "DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells". Regulatory Peptides. 137 (3): 147–55. doi:10.1016/j.regpep.2006.07.003. PMID 16908079.
  10. ↑ Wesley UV, McGroarty M, Homoyouni A (February 2005). "Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway". Cancer Research. 65 (4): 1325–34. doi:10.1158/0008-5472.CAN-04-1852. PMID 15735018.
  11. ↑ Busek P, Malík R, Sedo A (March 2004). "Dipeptidyl peptidase IV activity and/or structure homologues (DASH) and their substrates in cancer". The International Journal of Biochemistry & Cell Biology. 36 (3): 408–21. PMID 14687920.
  12. ↑ Kaji K, Yoshiji H, Ikenaka Y, Noguchi R, Aihara Y, Douhara A, Moriya K, Kawaratani H, Shirai Y, Yoshii J, Yanase K, Kitade M, Namisaki T, Fukui H (March 2014). "Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats". Journal of Gastroenterology. 49 (3): 481–91. doi:10.1007/s00535-013-0783-4. PMID 23475323.
  13. ↑ Min HS, Kim JE, Lee MH, Song HK, Kang YS, Lee MJ, Lee JE, Kim HW, Cha JJ, Chung YY, Hyun YY, Han JY, Cha DR (June 2014). "Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction". Laboratory Investigation; A Journal of Technical Methods and Pathology. 94 (6): 598–607. doi:10.1038/labinvest.2014.50. PMID 24687121.
  14. ↑ Havre PA, Abe M, Urasaki Y, Ohnuma K, Morimoto C, Dang NH (January 2008). "The role of CD26/dipeptidyl peptidase IV in cancer". Frontiers in Bioscience. 13 (13): 1634–45. doi:10.2741/2787. PMID 17981655.
  15. ↑ Rosenstock J, Zinman B (April 2007). "Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus". Current Opinion in Endocrinology, Diabetes, and Obesity. 14 (2): 98–107. doi:10.1097/MED.0b013e3280a02f65. PMID 17940427.
  16. ↑ Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL (March 2013). "Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC". Nature. ScienceNews. 495 (7440): 251–4. doi:10.1038/nature12005. PMID 23486063. Lay summary – ScienceNews.

Further reading

  • Ansorge S, Bühling F, Kähne T, Lendeckel U, Reinhold D, Täger M, Wrenger S (1997). "CD26/dipeptidyl peptidase IV in lymphocyte growth regulation". Advances in Experimental Medicine and Biology. 421: 127–40. doi:10.1007/978-1-4757-9613-1_17. PMID 9330689.
  • Reinhold D, Kähne T, Steinbrecher A, Wrenger S, Neubert K, Ansorge S, Brocke S (2003). "The role of dipeptidyl peptidase IV (DP IV) enzymatic activity in T cell activation and autoimmunity". Biological Chemistry. 383 (7–8): 1133–8. doi:10.1515/BC.2002.123. PMID 12437097.
  • Sato K, Dang NH (March 2003). "CD26: a novel treatment target for T-cell lymphoid malignancies? (Review)". International Journal of Oncology. 22 (3): 481–97. doi:10.3892/ijo.22.3.481. PMID 12579300.
  • de Meester I, Lambeir AM, Proost P, Scharpé S (2003). "Dipeptidyl peptidase IV substrates. An update on in vitro peptide hydrolysis by human DPPIV". Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology. 524: 3–17. doi:10.1007/0-306-47920-6_1. ISBN 0-306-47717-3. PMID 12675218.
  • Koch S, Anthonsen D, Skovbjerg H, Sjöström H (2003). "On the role of dipeptidyl peptidase IV in the digestion of an immunodominant epitope in celiac disease". Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology. 524: 181–7. doi:10.1007/0-306-47920-6_22. ISBN 0-306-47717-3. PMID 12675238.
  • Pro B, Dang NH (October 2004). "CD26/dipeptidyl peptidase IV and its role in cancer". Histology and Histopathology. 19 (4): 1345–51. doi:10.14670/HH-19.1345. PMID 15375776.

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Dipeptidyl_peptidase-4&oldid=1531540"