PSMD6: Difference between revisions

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imported>Graeme Bartlett
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{{Infobox_gene}}
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'''26S proteasome non-ATPase regulatory subunit 6''' is an [[enzyme]] that in humans is encoded by the ''PSMD6'' [[gene]].<ref name="pmid10723133">{{cite journal | vauthors = Ren S, Smith MJ, Louro ID, McKie-Bell P, Bani MR, Wagner M, Zochodne B, Redden DT, Grizzle WE, ((Wang Nd)), Smith DI, Herbst RA, Bardenheuer W, Opalka B, Schütte J, Trent JM, Ben-David Y, Ruppert JM | title = The p44S10 locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma | journal = Oncogene | volume = 19 | issue = 11 | pages = 1419–27 | date = Mar 2000 | pmid = 10723133 | pmc =  | doi = 10.1038/sj.onc.1203462 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PSMD6 proteasome (prosome, macropain) 26S subunit, non-ATPase, 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9861| accessdate = }}</ref>
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| update_protein_box = yes
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== Clinical significance ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = Proteasome (prosome, macropain) 26S subunit, non-ATPase, 6
| HGNCid = 9564
| Symbol = PSMD6
| AltSymbols =; S10; KIAA0107; SGA-113M; p44S10
| OMIM = 
| ECnumber = 
| Homologene = 7157
| MGIid = 1913663
| GeneAtlas_image1 = PBB_GE_PSMD6_202753_at_tn.png
| Function = {{GNF_GO|id=GO:0016887 |text = ATPase activity}}
| Component = {{GNF_GO|id=GO:0000502 |text = proteasome complex (sensu Eukaryota)}} {{GNF_GO|id=GO:0005829 |text = cytosol}}
| Process = {{GNF_GO|id=GO:0006510 |text = ATP-dependent proteolysis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 9861
    | Hs_Ensembl = ENSG00000163636
    | Hs_RefseqProtein = NP_055629
    | Hs_RefseqmRNA = NM_014814
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 3
    | Hs_GenLoc_start = 63971271
    | Hs_GenLoc_end = 63984189
    | Hs_Uniprot = Q15008
    | Mm_EntrezGene = 66413
    | Mm_Ensembl = ENSMUSG00000021737
    | Mm_RefseqmRNA = NM_025550
    | Mm_RefseqProtein = NP_079826
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 14
    | Mm_GenLoc_start = 12905451
    | Mm_GenLoc_end = 12914207
    | Mm_Uniprot = Q8C1T2
  }}
}}
'''Proteasome (prosome, macropain) 26S subunit, non-ATPase, 6''', also known as '''PSMD6''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PSMD6 proteasome (prosome, macropain) 26S subunit, non-ATPase, 6| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9861| accessdate = }}</ref>


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The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future.
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==References==
The proteasomes form a pivotal component for the [[proteasome|Ubiquitin-Proteasome System (UPS)]] <ref>{{cite journal | vauthors = Kleiger G, Mayor T | title = Perilous journey: a tour of the ubiquitin-proteasome system | journal = Trends in Cell Biology | volume = 24 | issue = 6 | pages = 352–9 | date = Jun 2014 | pmid = 24457024 | pmc = 4037451 | doi = 10.1016/j.tcb.2013.12.003 }}</ref> and corresponding cellular Protein Quality Control (PQC). Protein [[ubiquitination]] and subsequent [[proteolysis]] and degradation by the proteasome are important mechanisms in the regulation of the [[cell cycle]], [[cell growth]] and differentiation, gene transcription, signal transduction and [[apoptosis]].<ref>{{cite journal | vauthors = Goldberg AL, Stein R, Adams J | title = New insights into proteasome function: from archaebacteria to drug development | journal = Chemistry & Biology | volume = 2 | issue = 8 | pages = 503–8 | date = Aug 1995 | pmid = 9383453 | doi=10.1016/1074-5521(95)90182-5}}</ref> Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,<ref>{{cite journal | vauthors = Sulistio YA, Heese K | title = The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer's Disease | journal = Molecular Neurobiology | date = Jan 2015 | pmid = 25561438 | doi = 10.1007/s12035-014-9063-4 | volume=53 | pages=905–31}}</ref><ref>{{cite journal | vauthors = Ortega Z, Lucas JJ | title = Ubiquitin-proteasome system involvement in Huntington's disease | journal = Frontiers in Molecular Neuroscience | volume = 7 | pages = 77 | date = 2014 | pmid = 25324717 | pmc = 4179678 | doi = 10.3389/fnmol.2014.00077 }}</ref> cardiovascular diseases,<ref>{{cite journal | vauthors = Sandri M, Robbins J | title = Proteotoxicity: an underappreciated pathology in cardiac disease | journal = Journal of Molecular and Cellular Cardiology | volume = 71 | pages = 3–10 | date = Jun 2014 | pmid = 24380730 | pmc = 4011959 | doi = 10.1016/j.yjmcc.2013.12.015 }}</ref><ref>{{cite journal | vauthors = Drews O, Taegtmeyer H | title = Targeting the ubiquitin-proteasome system in heart disease: the basis for new therapeutic strategies | journal = Antioxidants & Redox Signaling | volume = 21 | issue = 17 | pages = 2322–43 | date = Dec 2014 | pmid = 25133688 | pmc = 4241867 | doi = 10.1089/ars.2013.5823 }}</ref><ref>{{cite journal | vauthors = Wang ZV, Hill JA | title = Protein quality control and metabolism: bidirectional control in the heart | journal = Cell Metabolism | volume = 21 | issue = 2 | pages = 215–26 | date = Feb 2015 | pmid = 25651176 | pmc = 4317573 | doi = 10.1016/j.cmet.2015.01.016 }}</ref> inflammatory responses and autoimmune diseases,<ref name="Karin M 2000">{{cite journal | vauthors = Karin M, Delhase M | title = The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling | journal = Seminars in Immunology | volume = 12 | issue = 1 | pages = 85–98 | date = Feb 2000 | pmid = 10723801 | doi = 10.1006/smim.2000.0210 }}</ref>  and systemic DNA damage responses leading to [[malignancies]].<ref>{{cite journal | vauthors = Ermolaeva MA, Dakhovnik A, Schumacher B | title = Quality control mechanisms in cellular and systemic DNA damage responses | journal = Ageing Research Reviews | volume = 23 | issue = Pt A | pages = 3–11 | date = Jan 2015 | pmid = 25560147 | doi = 10.1016/j.arr.2014.12.009 | pmc=4886828}}</ref>
{{reflist|2}}
 
==Further reading==
Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including [[Alzheimer's disease]],<ref>{{cite journal | vauthors = Checler F, da Costa CA, Ancolio K, Chevallier N, Lopez-Perez E, Marambaud P | title = Role of the proteasome in Alzheimer's disease | journal = Biochimica et Biophysica Acta | volume = 1502 | issue = 1 | pages = 133–8 | date = Jul 2000 | pmid = 10899438 | doi=10.1016/s0925-4439(00)00039-9}}</ref> [[Parkinson's disease]]<ref name="ReferenceC">{{cite journal | vauthors = Chung KK, Dawson VL, Dawson TM | title = The role of the ubiquitin-proteasomal pathway in Parkinson's disease and other neurodegenerative disorders | journal = Trends in Neurosciences | volume = 24 | issue = 11 Suppl | pages = S7–14 | date = Nov 2001 | pmid = 11881748 | doi=10.1016/s0166-2236(00)01998-6}}</ref> and [[Pick's disease]],<ref name="ReferenceB">{{cite journal | vauthors = Ikeda K, Akiyama H, Arai T, Ueno H, Tsuchiya K, Kosaka K | title = Morphometrical reappraisal of motor neuron system of Pick's disease and amyotrophic lateral sclerosis with dementia | journal = Acta Neuropathologica | volume = 104 | issue = 1 | pages = 21–8 | date = Jul 2002 | pmid = 12070660 | doi = 10.1007/s00401-001-0513-5 }}</ref> [[Amyotrophic lateral sclerosis]] ([[ALS]]),<ref name="ReferenceB"/> [[Huntington's disease]],<ref name="ReferenceC"/> [[Creutzfeldt–Jakob disease]],<ref>{{cite journal | vauthors = Manaka H, Kato T, Kurita K, Katagiri T, Shikama Y, Kujirai K, Kawanami T, Suzuki Y, Nihei K, Sasaki H | title = Marked increase in cerebrospinal fluid ubiquitin in Creutzfeldt–Jakob disease | journal = Neuroscience Letters | volume = 139 | issue = 1 | pages = 47–9 | date = May 1992 | pmid = 1328965 | doi=10.1016/0304-3940(92)90854-z}}</ref> and motor neuron diseases, polyglutamine (PolyQ) diseases, [[Muscular dystrophies]]<ref>{{cite journal | vauthors = Mathews KD, Moore SA | title = Limb-girdle muscular dystrophy | journal = Current Neurology and Neuroscience Reports | volume = 3 | issue = 1 | pages = 78–85 | date = Jan 2003 | pmid = 12507416 | doi=10.1007/s11910-003-0042-9}}</ref> and several rare forms of neurodegenerative diseases associated with [[dementia]].<ref>{{cite journal | vauthors = Mayer RJ | title = From neurodegeneration to neurohomeostasis: the role of ubiquitin | journal = Drug News & Perspectives | volume = 16 | issue = 2 | pages = 103–8 | date = Mar 2003 | pmid = 12792671 | doi=10.1358/dnp.2003.16.2.829327}}</ref> As part of the [[proteasome|Ubiquitin-Proteasome System (UPS)]], the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac [[Ischemic]] injury,<ref>{{cite journal | vauthors = Calise J, Powell SR | title = The ubiquitin proteasome system and myocardial ischemia | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 304 | issue = 3 | pages = H337–49 | date = Feb 2013 | pmid = 23220331 | pmc = 3774499 | doi = 10.1152/ajpheart.00604.2012 }}</ref> [[ventricular hypertrophy]]<ref>{{cite journal | vauthors = Predmore JM, Wang P, Davis F, Bartolone S, Westfall MV, Dyke DB, Pagani F, Powell SR, Day SM | title = Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies | journal = Circulation | volume = 121 | issue = 8 | pages = 997–1004 | date = Mar 2010 | pmid = 20159828 | pmc = 2857348 | doi = 10.1161/CIRCULATIONAHA.109.904557 }}</ref> and [[Heart failure]].<ref>{{cite journal | vauthors = Powell SR | title = The ubiquitin-proteasome system in cardiac physiology and pathology | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 291 | issue = 1 | pages = H1–H19 | date = Jul 2006 | pmid = 16501026 | doi = 10.1152/ajpheart.00062.2006 }}</ref> Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of [[transcription factors]], such as [[p53]], [[c-Jun]], [[c-Fos]], [[NF-κB]], [[c-Myc]], HIF-1α, MATα2, [[STAT3]], sterol-regulated element-binding proteins and [[androgen receptors]] are all controlled by the UPS and thus involved in the development of various malignancies.<ref>{{cite journal | vauthors = Adams J | title = Potential for proteasome inhibition in the treatment of cancer | journal = Drug Discovery Today | volume = 8 | issue = 7 | pages = 307–15 | date = Apr 2003 | pmid = 12654543 | doi=10.1016/s1359-6446(03)02647-3}}</ref> Moreover, the UPS regulates the degradation of tumor suppressor gene products such as [[adenomatous polyposis coli]] ([[adenomatous polyposis coli|APC]]) in colorectal cancer, [[retinoblastoma]] (Rb). and [[von Hippel-Lindau tumor suppressor]] (VHL), as well as a number of [[proto-oncogenes]] ([[Raf kinase|Raf]], [[Myc]], [[MYB (gene)|Myb]], [[NF-κB|Rel]], [[Src (gene)|Src]], [[MOS (gene)|Mos]], [[Abl (gene)|Abl]]). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory [[cytokines]] such as [[TNF-α]], IL-β, [[Interleukin 8|IL-8]], [[adhesion molecules]] ([[ICAM-1]], [[VCAM-1]], [[P-selectin]]) and [[prostaglandins]] and [[nitric oxide]] (NO).<ref name="Karin M 2000"/> Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of [[Cyclin-dependent kinase|CDK]] inhibitors.<ref>{{cite journal | vauthors = Ben-Neriah Y | title = Regulatory functions of ubiquitination in the immune system | journal = Nature Immunology | volume = 3 | issue = 1 | pages = 20–6 | date = Jan 2002 | pmid = 11753406 | doi = 10.1038/ni0102-20 }}</ref> Lastly, [[autoimmune disease]] patients with [[Systemic lupus erythematosus|SLE]], [[Sjogren's syndrome]] and [[rheumatoid arthritis]] (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.<ref>{{cite journal | vauthors = Egerer K, Kuckelkorn U, Rudolph PE, Rückert JC, Dörner T, Burmester GR, Kloetzel PM, Feist E | title = Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseases | journal = The Journal of Rheumatology | volume = 29 | issue = 10 | pages = 2045–52 | date = Oct 2002 | pmid = 12375310 }}</ref>
{{refbegin | 2}}
 
{{PBB_Further_reading
During the antigen processing for the major histocompatibility complex (MHC) class-I,  the proteasome is the major degradation machinery that degrades the antigen and present the resulting peptides to cytotoxic T lymphocytes.<ref>{{cite journal | vauthors = Basler M, Lauer C, Beck U, Groettrup M | title = The proteasome inhibitor bortezomib enhances the susceptibility to viral infection | journal = Journal of Immunology | volume = 183 | issue = 10 | pages = 6145–50 | date = Nov 2009 | pmid = 19841190 | doi = 10.4049/jimmunol.0901596 }}</ref><ref>{{cite journal | vauthors = Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL | title = Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules | journal = Cell | volume = 78 | issue = 5 | pages = 761–71 | date = Sep 1994 | pmid = 8087844 | doi=10.1016/s0092-8674(94)90462-6}}</ref> The immunoproteasome has been considered playing a critical role in improving the quality and quantity of generated class-I ligands.
| citations =  
 
*{{cite journal  | author=Goff SP |title=Death by deamination: a novel host restriction system for HIV-1. |journal=Cell |volume=114 |issue= 3 |pages= 281-3 |year= 2003 |pmid= 12914693 |doi=  }}
== Interactions ==
*{{cite journal | author=Nagase T, Miyajima N, Tanaka A, ''et al.'' |title=Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1. |journal=DNA Res. |volume=2 |issue= 1 |pages= 37-43 |year= 1995 |pmid= 7788527 |doi= }}
 
*{{cite journal | author=Seeger M, Ferrell K, Frank R, Dubiel W |title=HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation. |journal=J. Biol. Chem. |volume=272 |issue= 13 |pages= 8145-8 |year= 1997 |pmid= 9079628 |doi= }}
PSMD6 has been shown to [[Protein-protein interaction|interact]] with [[PSMD13]].<ref name=pmid17353931>{{cite journal | vauthors = Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D | title = Large-scale mapping of human protein–protein interactions by mass spectrometry | journal = Mol. Syst. Biol. | volume = 3 | issue = 1 | pages = 89 | year = 2007 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 }}</ref>
*{{cite journal | author=Madani N, Kabat D |title=An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein. |journal=J. Virol. |volume=72 |issue= 12 |pages= 10251-5 |year= 1998 |pmid= 9811770 |doi= }}
 
*{{cite journal | author=Simon JH, Gaddis NC, Fouchier RA, Malim MH |title=Evidence for a newly discovered cellular anti-HIV-1 phenotype. |journal=Nat. Med. |volume=4 |issue= 12 |pages= 1397-400 |year= 1998 |pmid= 9846577 |doi= 10.1038/3987 }}
== References ==
*{{cite journal | author=Ren S, Smith MJ, Louro ID, ''et al.'' |title=The p44S10 locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma. |journal=Oncogene |volume=19 |issue= 11 |pages= 1419-27 |year= 2000 |pmid= 10723133 |doi= 10.1038/sj.onc.1203462 }}
{{reflist|33em}}
*{{cite journal | author=Mulder LC, Muesing MA |title=Degradation of HIV-1 integrase by the N-end rule pathway. |journal=J. Biol. Chem. |volume=275 |issue= 38 |pages= 29749-53 |year= 2000 |pmid= 10893419 |doi= 10.1074/jbc.M004670200 }}
 
*{{cite journal | author=Sheehy AM, Gaddis NC, Choi JD, Malim MH |title=Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. |journal=Nature |volume=418 |issue= 6898 |pages= 646-50 |year= 2002 |pmid= 12167863 |doi= 10.1038/nature00939 }}
== Further reading ==
*{{cite journal | author=Huang X, Seifert U, Salzmann U, ''et al.'' |title=The RTP site shared by the HIV-1 Tat protein and the 11S regulator subunit alpha is crucial for their effects on proteasome function including antigen processing. |journal=J. Mol. Biol. |volume=323 |issue= 4 |pages= 771-82 |year= 2002 |pmid= 12419264 |doi= }}
{{refbegin|33em}}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |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 }}
* {{cite journal | vauthors = Goff SP | title = Death by deamination: a novel host restriction system for HIV-1 | journal = Cell | volume = 114 | issue = 3 | pages = 281–3 | year = 2003 | pmid = 12914693 | doi = 10.1016/S0092-8674(03)00602-0 }}
*{{cite journal | author=Gaddis NC, Chertova E, Sheehy AM, ''et al.'' |title=Comprehensive investigation of the molecular defect in vif-deficient human immunodeficiency virus type 1 virions. |journal=J. Virol. |volume=77 |issue= 10 |pages= 5810-20 |year= 2003 |pmid= 12719574 |doi= }}
* {{cite journal | vauthors = Nagase T, Miyajima N, Tanaka A, Sazuka T, Seki N, Sato S, Tabata S, Ishikawa K, Kawarabayasi Y, Kotani H | title = Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1 | journal = DNA Res. | volume = 2 | issue = 1 | pages = 37–43 | year = 1995 | pmid = 7788527 | doi = 10.1093/dnares/2.1.37 }}
*{{cite journal | author=Lecossier D, Bouchonnet F, Clavel F, Hance AJ |title=Hypermutation of HIV-1 DNA in the absence of the Vif protein. |journal=Science |volume=300 |issue= 5622 |pages= 1112 |year= 2003 |pmid= 12750511 |doi= 10.1126/science.1083338 }}
* {{cite journal | vauthors = Seeger M, Ferrell K, Frank R, Dubiel W | title = HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation | journal = J. Biol. Chem. | volume = 272 | issue = 13 | pages = 8145–8 | year = 1997 | pmid = 9079628 | doi = 10.1074/jbc.272.13.8145 }}
*{{cite journal | author=Zhang H, Yang B, Pomerantz RJ, ''et al.'' |title=The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. |journal=Nature |volume=424 |issue= 6944 |pages= 94-8 |year= 2003 |pmid= 12808465 |doi= 10.1038/nature01707 }}
* {{cite journal | vauthors = Madani N, Kabat D | title = An Endogenous Inhibitor of Human Immunodeficiency Virus in Human Lymphocytes Is Overcome by the Viral Vif Protein | journal = J. Virol. | volume = 72 | issue = 12 | pages = 10251–5 | year = 1998 | pmid = 9811770 | pmc = 110608 | doi =  }}
*{{cite journal | author=Mangeat B, Turelli P, Caron G, ''et al.'' |title=Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. |journal=Nature |volume=424 |issue= 6944 |pages= 99-103 |year= 2003 |pmid= 12808466 |doi= 10.1038/nature01709 }}
* {{cite journal | vauthors = Simon JH, Gaddis NC, Fouchier RA, Malim MH | title = Evidence for a newly discovered cellular anti-HIV-1 phenotype | journal = Nat. Med. | volume = 4 | issue = 12 | pages = 1397–400 | year = 1998 | pmid = 9846577 | doi = 10.1038/3987 }}
*{{cite journal | author=Harris RS, Bishop KN, Sheehy AM, ''et al.'' |title=DNA deamination mediates innate immunity to retroviral infection. |journal=Cell |volume=113 |issue= 6 |pages= 803-9 |year= 2003 |pmid= 12809610 |doi= }}
* {{cite journal | vauthors = Mulder LC, Muesing MA | title = Degradation of HIV-1 integrase by the N-end rule pathway | journal = J. Biol. Chem. | volume = 275 | issue = 38 | pages = 29749–53 | year = 2000 | pmid = 10893419 | doi = 10.1074/jbc.M004670200 }}
*{{cite journal | author=Harris RS, Sheehy AM, Craig HM, ''et al.'' |title=DNA deamination: not just a trigger for antibody diversification but also a mechanism for defense against retroviruses. |journal=Nat. Immunol. |volume=4 |issue= 7 |pages= 641-3 |year= 2003 |pmid= 12830140 |doi= 10.1038/ni0703-641 }}
* {{cite journal | vauthors = Sheehy AM, Gaddis NC, Choi JD, Malim MH | title = Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein | journal = Nature | volume = 418 | issue = 6898 | pages = 646–50 | year = 2002 | pmid = 12167863 | doi = 10.1038/nature00939 | bibcode = 2002Natur.418..646S }}
*{{cite journal | author=Gu Y, Sundquist WI |title=Good to CU. |journal=Nature |volume=424 |issue= 6944 |pages= 21-2 |year= 2003 |pmid= 12840737 |doi= 10.1038/424021a }}
* {{cite journal | vauthors = Huang X, Seifert U, Salzmann U, Henklein P, Preissner R, Henke W, Sijts AJ, Kloetzel PM, Dubiel W | title = The RTP site shared by the HIV-1 Tat protein and the 11S regulator subunit alpha is crucial for their effects on proteasome function including antigen processing | journal = J. Mol. Biol. | volume = 323 | issue = 4 | pages = 771–82 | year = 2002 | pmid = 12419264 | doi = 10.1016/S0022-2836(02)00998-1 }}
*{{cite journal  | author=Mariani R, Chen D, Schröfelbauer B, ''et al.'' |title=Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. |journal=Cell |volume=114 |issue= 1 |pages= 21-31 |year= 2003 |pmid= 12859895 |doi=  }}
* {{cite journal | vauthors = Gaddis NC, Chertova E, Sheehy AM, Henderson LE, Malim MH | title = Comprehensive Investigation of the Molecular Defect in vif-Deficient Human Immunodeficiency Virus Type 1 Virions | journal = J. Virol. | volume = 77 | issue = 10 | pages = 5810–20 | year = 2003 | pmid = 12719574 | pmc = 154025 | doi = 10.1128/JVI.77.10.5810-5820.2003 }}
*{{cite journal | author=KewalRamani VN, Coffin JM |title=Virology. Weapons of mutational destruction. |journal=Science |volume=301 |issue= 5635 |pages= 923-5 |year= 2003 |pmid= 12920286 |doi= 10.1126/science.1088965 }}
* {{cite journal | vauthors = Lecossier D, Bouchonnet F, Clavel F, Hance AJ | title = Hypermutation of HIV-1 DNA in the absence of the Vif protein | journal = Science | volume = 300 | issue = 5622 | pages = 1112 | year = 2003 | pmid = 12750511 | doi = 10.1126/science.1083338 }}
}}
* {{cite journal | vauthors = Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L | title = The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA | journal = Nature | volume = 424 | issue = 6944 | pages = 94–8 | year = 2003 | pmid = 12808465 | pmc = 1350966 | doi = 10.1038/nature01707 | bibcode = 2003Natur.424...94Z }}
* {{cite journal | vauthors = Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D | title = Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts | journal = Nature | volume = 424 | issue = 6944 | pages = 99–103 | year = 2003 | pmid = 12808466 | doi = 10.1038/nature01709 | bibcode = 2003Natur.424...99M }}
* {{cite journal | vauthors = Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim MH | title = DNA deamination mediates innate immunity to retroviral infection | journal = Cell | volume = 113 | issue = 6 | pages = 803–9 | year = 2003 | pmid = 12809610 | doi = 10.1016/S0092-8674(03)00423-9 }}
* {{cite journal | vauthors = Harris RS, Sheehy AM, Craig HM, Malim MH, Neuberger MS | title = DNA deamination: not just a trigger for antibody diversification but also a mechanism for defense against retroviruses | journal = Nat. Immunol. | volume = 4 | issue = 7 | pages = 641–3 | year = 2003 | pmid = 12830140 | doi = 10.1038/ni0703-641 }}
* {{cite journal | vauthors = Gu Y, Sundquist WI | title = Good to CU | journal = Nature | volume = 424 | issue = 6944 | pages = 21–2 | year = 2003 | pmid = 12840737 | doi = 10.1038/424021a | bibcode = 2003Natur.424...21G }}
* {{cite journal | vauthors = Mariani R, Chen D, Schröfelbauer B, Navarro F, König R, Bollman B, Münk C, Nymark-McMahon H, Landau NR | title = Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif | journal = Cell | volume = 114 | issue = 1 | pages = 21–31 | year = 2003 | pmid = 12859895 | doi = 10.1016/S0092-8674(03)00515-4 }}
* {{cite journal | vauthors = KewalRamani VN, Coffin JM | title = Virology. Weapons of mutational destruction | journal = Science | volume = 301 | issue = 5635 | pages = 923–5 | year = 2003 | pmid = 12920286 | doi = 10.1126/science.1088965 }}
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{{protein-stub}}
{{Proteasome subunits}}
{{WikiDoc Sources}}

Latest revision as of 12:10, 28 September 2018

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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26S proteasome non-ATPase regulatory subunit 6 is an enzyme that in humans is encoded by the PSMD6 gene.[1][2]

Clinical significance

The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future.

The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) [3] and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis.[4] Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,[5][6] cardiovascular diseases,[7][8][9] inflammatory responses and autoimmune diseases,[10] and systemic DNA damage responses leading to malignancies.[11]

Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease,[12] Parkinson's disease[13] and Pick's disease,[14] Amyotrophic lateral sclerosis (ALS),[14] Huntington's disease,[13] Creutzfeldt–Jakob disease,[15] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[16] and several rare forms of neurodegenerative diseases associated with dementia.[17] As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury,[18] ventricular hypertrophy[19] and Heart failure.[20] Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.[21] Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO).[10] Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors.[22] Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[23]

During the antigen processing for the major histocompatibility complex (MHC) class-I, the proteasome is the major degradation machinery that degrades the antigen and present the resulting peptides to cytotoxic T lymphocytes.[24][25] The immunoproteasome has been considered playing a critical role in improving the quality and quantity of generated class-I ligands.

Interactions

PSMD6 has been shown to interact with PSMD13.[26]

References

  1. ↑ Ren S, Smith MJ, Louro ID, McKie-Bell P, Bani MR, Wagner M, Zochodne B, Redden DT, Grizzle WE, Wang Nd, Smith DI, Herbst RA, Bardenheuer W, Opalka B, Schütte J, Trent JM, Ben-David Y, Ruppert JM (Mar 2000). "The p44S10 locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma". Oncogene. 19 (11): 1419–27. doi:10.1038/sj.onc.1203462. PMID 10723133.
  2. ↑ "Entrez Gene: PSMD6 proteasome (prosome, macropain) 26S subunit, non-ATPase, 6".
  3. ↑ Kleiger G, Mayor T (Jun 2014). "Perilous journey: a tour of the ubiquitin-proteasome system". Trends in Cell Biology. 24 (6): 352–9. doi:10.1016/j.tcb.2013.12.003. PMC 4037451. PMID 24457024.
  4. ↑ Goldberg AL, Stein R, Adams J (Aug 1995). "New insights into proteasome function: from archaebacteria to drug development". Chemistry & Biology. 2 (8): 503–8. doi:10.1016/1074-5521(95)90182-5. PMID 9383453.
  5. ↑ Sulistio YA, Heese K (Jan 2015). "The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer's Disease". Molecular Neurobiology. 53: 905–31. doi:10.1007/s12035-014-9063-4. PMID 25561438.
  6. ↑ Ortega Z, Lucas JJ (2014). "Ubiquitin-proteasome system involvement in Huntington's disease". Frontiers in Molecular Neuroscience. 7: 77. doi:10.3389/fnmol.2014.00077. PMC 4179678. PMID 25324717.
  7. ↑ Sandri M, Robbins J (Jun 2014). "Proteotoxicity: an underappreciated pathology in cardiac disease". Journal of Molecular and Cellular Cardiology. 71: 3–10. doi:10.1016/j.yjmcc.2013.12.015. PMC 4011959. PMID 24380730.
  8. ↑ Drews O, Taegtmeyer H (Dec 2014). "Targeting the ubiquitin-proteasome system in heart disease: the basis for new therapeutic strategies". Antioxidants & Redox Signaling. 21 (17): 2322–43. doi:10.1089/ars.2013.5823. PMC 4241867. PMID 25133688.
  9. ↑ Wang ZV, Hill JA (Feb 2015). "Protein quality control and metabolism: bidirectional control in the heart". Cell Metabolism. 21 (2): 215–26. doi:10.1016/j.cmet.2015.01.016. PMC 4317573. PMID 25651176.
  10. ↑ 10.0 10.1 Karin M, Delhase M (Feb 2000). "The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling". Seminars in Immunology. 12 (1): 85–98. doi:10.1006/smim.2000.0210. PMID 10723801.
  11. ↑ Ermolaeva MA, Dakhovnik A, Schumacher B (Jan 2015). "Quality control mechanisms in cellular and systemic DNA damage responses". Ageing Research Reviews. 23 (Pt A): 3–11. doi:10.1016/j.arr.2014.12.009. PMC 4886828. PMID 25560147.
  12. ↑ Checler F, da Costa CA, Ancolio K, Chevallier N, Lopez-Perez E, Marambaud P (Jul 2000). "Role of the proteasome in Alzheimer's disease". Biochimica et Biophysica Acta. 1502 (1): 133–8. doi:10.1016/s0925-4439(00)00039-9. PMID 10899438.
  13. ↑ 13.0 13.1 Chung KK, Dawson VL, Dawson TM (Nov 2001). "The role of the ubiquitin-proteasomal pathway in Parkinson's disease and other neurodegenerative disorders". Trends in Neurosciences. 24 (11 Suppl): S7–14. doi:10.1016/s0166-2236(00)01998-6. PMID 11881748.
  14. ↑ 14.0 14.1 Ikeda K, Akiyama H, Arai T, Ueno H, Tsuchiya K, Kosaka K (Jul 2002). "Morphometrical reappraisal of motor neuron system of Pick's disease and amyotrophic lateral sclerosis with dementia". Acta Neuropathologica. 104 (1): 21–8. doi:10.1007/s00401-001-0513-5. PMID 12070660.
  15. ↑ Manaka H, Kato T, Kurita K, Katagiri T, Shikama Y, Kujirai K, Kawanami T, Suzuki Y, Nihei K, Sasaki H (May 1992). "Marked increase in cerebrospinal fluid ubiquitin in Creutzfeldt–Jakob disease". Neuroscience Letters. 139 (1): 47–9. doi:10.1016/0304-3940(92)90854-z. PMID 1328965.
  16. ↑ Mathews KD, Moore SA (Jan 2003). "Limb-girdle muscular dystrophy". Current Neurology and Neuroscience Reports. 3 (1): 78–85. doi:10.1007/s11910-003-0042-9. PMID 12507416.
  17. ↑ Mayer RJ (Mar 2003). "From neurodegeneration to neurohomeostasis: the role of ubiquitin". Drug News & Perspectives. 16 (2): 103–8. doi:10.1358/dnp.2003.16.2.829327. PMID 12792671.
  18. ↑ Calise J, Powell SR (Feb 2013). "The ubiquitin proteasome system and myocardial ischemia". American Journal of Physiology. Heart and Circulatory Physiology. 304 (3): H337–49. doi:10.1152/ajpheart.00604.2012. PMC 3774499. PMID 23220331.
  19. ↑ Predmore JM, Wang P, Davis F, Bartolone S, Westfall MV, Dyke DB, Pagani F, Powell SR, Day SM (Mar 2010). "Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies". Circulation. 121 (8): 997–1004. doi:10.1161/CIRCULATIONAHA.109.904557. PMC 2857348. PMID 20159828.
  20. ↑ Powell SR (Jul 2006). "The ubiquitin-proteasome system in cardiac physiology and pathology". American Journal of Physiology. Heart and Circulatory Physiology. 291 (1): H1–H19. doi:10.1152/ajpheart.00062.2006. PMID 16501026.
  21. ↑ Adams J (Apr 2003). "Potential for proteasome inhibition in the treatment of cancer". Drug Discovery Today. 8 (7): 307–15. doi:10.1016/s1359-6446(03)02647-3. PMID 12654543.
  22. ↑ Ben-Neriah Y (Jan 2002). "Regulatory functions of ubiquitination in the immune system". Nature Immunology. 3 (1): 20–6. doi:10.1038/ni0102-20. PMID 11753406.
  23. ↑ Egerer K, Kuckelkorn U, Rudolph PE, Rückert JC, Dörner T, Burmester GR, Kloetzel PM, Feist E (Oct 2002). "Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseases". The Journal of Rheumatology. 29 (10): 2045–52. PMID 12375310.
  24. ↑ Basler M, Lauer C, Beck U, Groettrup M (Nov 2009). "The proteasome inhibitor bortezomib enhances the susceptibility to viral infection". Journal of Immunology. 183 (10): 6145–50. doi:10.4049/jimmunol.0901596. PMID 19841190.
  25. ↑ Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL (Sep 1994). "Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules". Cell. 78 (5): 761–71. doi:10.1016/s0092-8674(94)90462-6. PMID 8087844.
  26. ↑ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.

Further reading

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