[{"@context":"http:\/\/schema.org\/","@type":"BlogPosting","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/psmd12-wikipedia\/#BlogPosting","mainEntityOfPage":"https:\/\/wiki.edu.vn\/en\/wiki24\/psmd12-wikipedia\/","headline":"PSMD12 – Wikipedia","name":"PSMD12 – Wikipedia","description":"From Wikipedia, the free encyclopedia Enzyme found in humans 26S proteasome non-ATPase regulatory subunit 12 is an enzyme that in","datePublished":"2021-11-10","dateModified":"2021-11-10","author":{"@type":"Person","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/#Person","name":"lordneo","url":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/","image":{"@type":"ImageObject","@id":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","height":96,"width":96}},"publisher":{"@type":"Organization","name":"Enzyklop\u00e4die","logo":{"@type":"ImageObject","@id":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","url":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","width":600,"height":60}},"image":{"@type":"ImageObject","@id":"https:\/\/en.wikipedia.org\/wiki\/Special:CentralAutoLogin\/start?type=1x1","url":"https:\/\/en.wikipedia.org\/wiki\/Special:CentralAutoLogin\/start?type=1x1","height":"1","width":"1"},"url":"https:\/\/wiki.edu.vn\/en\/wiki24\/psmd12-wikipedia\/","about":["Wiki"],"wordCount":10895,"articleBody":"From Wikipedia, the free encyclopediaEnzyme found in humans26S proteasome non-ATPase regulatory subunit 12 is an enzyme that in humans is encoded by the PSMD12 gene.[5]Table of ContentsFunction[edit]Clinical significance[edit]References[edit]Further reading[edit]Function[edit]The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP\/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 3.[6]Clinical significance[edit]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\u2013proteasome system (UPS) [7] 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.[8] 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,[9][10] cardiovascular diseases,[11][12][13] inflammatory responses and autoimmune diseases,[14]  and systemic DNA damage responses leading to malignancies.[15]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,[16]Parkinson’s disease[17] and Pick’s disease,[18]Amyotrophic lateral sclerosis (ALS),[18]Huntington’s disease,[17]Creutzfeldt\u2013Jakob disease,[19] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[20] and several rare forms of neurodegenerative diseases associated with dementia.[21] As part of the ubiquitin\u2013proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury,[22]ventricular hypertrophy[23] and heart failure.[24] 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-\u03baB, c-Myc, HIF-1\u03b1, MAT\u03b12, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.[25] 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\u2013Lindau 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-\u03baB which further regulates the expression of pro inflammatory cytokines such as TNF-\u03b1, IL-\u03b2, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO).[14] 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.[26] Lastly, autoimmune disease patients with SLE, Sj\u00f6gren syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[27]Gene expression levels of the proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 patients with neuroendocrine pulmonary tumors and compared to controls. The study reviled that PSMB4 mRNA was significantly associated with proliferative activity of neuroendocrine pulmonary tumors.[28] However, a role of PSMA5 was also indicated in neuroendocrine pulmonary tumors. The PSMA5 protein has further been associated with the biosynthesis of conjugated linoleic acid (CLA) in mammary tissue.[29]References[edit]^ a b c GRCh38: Ensembl release 89: ENSG00000197170 – Ensembl, May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020720 – Ensembl, May 2017^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.^ “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.^ Saito A, Watanabe TK, Shimada Y, Fujiwara T, Slaughter CA, DeMartino GN, Tanahashi N, Tanaka K (Dec 1997). “cDNA cloning and functional analysis of p44.5 and p55, two regulatory subunits of the 26S proteasome”. Gene. 203 (2): 241\u201350. doi:10.1016\/S0378-1119(97)00524-6. PMID\u00a09426256.^ “Entrez Gene: PSMD12 proteasome (prosome, macropain) 26S subunit, non-ATPase, 12”.^ Kleiger G, Mayor T (Jun 2014). “Perilous journey: a tour of the ubiquitin\u2013proteasome system”. Trends in Cell Biology. 24 (6): 352\u20139. doi:10.1016\/j.tcb.2013.12.003. PMC\u00a04037451. PMID\u00a024457024.^ Goldberg AL, Stein R, Adams J (Aug 1995). “New insights into proteasome function: from archaebacteria to drug development”. Chemistry & Biology. 2 (8): 503\u20138. doi:10.1016\/1074-5521(95)90182-5. PMID\u00a09383453.^ Sulistio YA, Heese K (Jan 2015). “The Ubiquitin\u2013Proteasome System and Molecular Chaperone Deregulation in Alzheimer’s Disease”. Molecular Neurobiology. 53 (2): 905\u201331. doi:10.1007\/s12035-014-9063-4. PMID\u00a025561438. S2CID\u00a014103185.^ Ortega Z, Lucas JJ (2014). “Ubiquitin\u2013proteasome system involvement in Huntington’s disease”. Frontiers in Molecular Neuroscience. 7: 77. doi:10.3389\/fnmol.2014.00077. PMC\u00a04179678. PMID\u00a025324717.^ Sandri M, Robbins J (Jun 2014). “Proteotoxicity: an underappreciated pathology in cardiac disease”. Journal of Molecular and Cellular Cardiology. 71: 3\u201310. doi:10.1016\/j.yjmcc.2013.12.015. PMC\u00a04011959. PMID\u00a024380730.^ 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\u201343. doi:10.1089\/ars.2013.5823. PMC\u00a04241867. PMID\u00a025133688.^ Wang ZV, Hill JA (Feb 2015). “Protein quality control and metabolism: bidirectional control in the heart”. Cell Metabolism. 21 (2): 215\u201326. doi:10.1016\/j.cmet.2015.01.016. PMC\u00a04317573. PMID\u00a025651176.^ a b 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\u201398. doi:10.1006\/smim.2000.0210. PMID\u00a010723801.^ Ermolaeva MA, Dakhovnik A, Schumacher B (Sep 2015). “Quality control mechanisms in cellular and systemic DNA damage responses”. Ageing Research Reviews. 23 (Pt A): 3\u201311. doi:10.1016\/j.arr.2014.12.009. PMC\u00a04886828. PMID\u00a025560147.^ 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 (BBA) – Molecular Basis of Disease. 1502 (1): 133\u20138. doi:10.1016\/s0925-4439(00)00039-9. PMID\u00a010899438.^ a b 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\u201314. doi:10.1016\/s0166-2236(00)01998-6. PMID\u00a011881748. S2CID\u00a02211658.^ a b 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\u20138. doi:10.1007\/s00401-001-0513-5. PMID\u00a012070660. S2CID\u00a022396490.^ 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\u2013Jakob disease”. Neuroscience Letters. 139 (1): 47\u20139. doi:10.1016\/0304-3940(92)90854-z. PMID\u00a01328965. S2CID\u00a028190967.^ Mathews KD, Moore SA (Jan 2003). “Limb-girdle muscular dystrophy”. Current Neurology and Neuroscience Reports. 3 (1): 78\u201385. doi:10.1007\/s11910-003-0042-9. PMID\u00a012507416. S2CID\u00a05780576.^ Mayer RJ (Mar 2003). “From neurodegeneration to neurohomeostasis: the role of ubiquitin”. Drug News & Perspectives. 16 (2): 103\u20138. doi:10.1358\/dnp.2003.16.2.829327. PMID\u00a012792671.^ Calise J, Powell SR (Feb 2013). “The ubiquitin proteasome system and myocardial ischemia”. American Journal of Physiology. Heart and Circulatory Physiology. 304 (3): H337\u201349. doi:10.1152\/ajpheart.00604.2012. PMC\u00a03774499. PMID\u00a023220331.^ 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\u20131004. doi:10.1161\/CIRCULATIONAHA.109.904557. PMC\u00a02857348. PMID\u00a020159828.^ Powell SR (Jul 2006). “The ubiquitin-proteasome system in cardiac physiology and pathology”. American Journal of Physiology. Heart and Circulatory Physiology. 291 (1): H1\u2013H19. doi:10.1152\/ajpheart.00062.2006. PMID\u00a016501026. S2CID\u00a07073263.^ Adams J (Apr 2003). “Potential for proteasome inhibition in the treatment of cancer”. Drug Discovery Today. 8 (7): 307\u201315. doi:10.1016\/s1359-6446(03)02647-3. PMID\u00a012654543.^ Ben-Neriah Y (Jan 2002). “Regulatory functions of ubiquitination in the immune system”. Nature Immunology. 3 (1): 20\u20136. doi:10.1038\/ni0102-20. PMID\u00a011753406. S2CID\u00a026973319.^ Egerer K, Kuckelkorn U, Rudolph PE, R\u00fcckert JC, D\u00f6rner 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\u201352. PMID\u00a012375310.^ Mairinger FD, Walter RF, Theegarten D, Hager T, Vollbrecht C, Christoph DC, Worm K, Ting S, Werner R, Stamatis G, Mairinger T, Baba H, Zarogoulidis K, Huang H, Li Q, Tsakiridis K, Zarogoulidis P, Schmid KW, Wohlschlaeger J (2014). “Gene Expression Analysis of the 26S Proteasome Subunit PSMB4 Reveals Significant Upregulation, Different Expression and Association with Proliferation in Human Pulmonary Neuroendocrine Tumours”. Journal of Cancer. 5 (8): 646\u201354. doi:10.7150\/jca.9955. PMC\u00a04142326. PMID\u00a025157275.^ Jin YC, Li ZH, Hong ZS, Xu CX, Han JA, Choi SH, Yin JL, Zhang QK, Lee KB, Kang SK, Song MK, Kim YJ, Kang HS, Choi YJ, Lee HG (Aug 2012). “Conjugated linoleic acid synthesis-related protein proteasome subunit \u03b1 5 (PSMA5) is increased by vaccenic acid treatment in goat mammary tissue”. Journal of Dairy Science. 95 (8): 4286\u201397. doi:10.3168\/jds.2011-4281. PMID\u00a022818443.Further reading[edit]Coux O, Tanaka K, Goldberg AL (1996). “Structure and functions of the 20S and 26S proteasomes”. Annual Review of Biochemistry. 65: 801\u201347. doi:10.1146\/annurev.bi.65.070196.004101. PMID\u00a08811196.Goff SP (Aug 2003). “Death by deamination: a novel host restriction system for HIV-1”. Cell. 114 (3): 281\u20133. doi:10.1016\/S0092-8674(03)00602-0. PMID\u00a012914693. S2CID\u00a016340355.Kanayama HO, Tamura T, Ugai S, Kagawa S, Tanahashi N, Yoshimura T, Tanaka K, Ichihara A (Jun 1992). “Demonstration that a human 26S proteolytic complex consists of a proteasome and multiple associated protein components and hydrolyzes ATP and ubiquitin-ligated proteins by closely linked mechanisms”. European Journal of Biochemistry. 206 (2): 567\u201378. doi:10.1111\/j.1432-1033.1992.tb16961.x. PMID\u00a01317798.Maruyama K, Sugano S (Jan 1994). “Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides”. Gene. 138 (1\u20132): 171\u20134. doi:10.1016\/0378-1119(94)90802-8. PMID\u00a08125298.Seeger M, Ferrell K, Frank R, Dubiel W (Mar 1997). “HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation”. The Journal of Biological Chemistry. 272 (13): 8145\u20138. doi:10.1074\/jbc.272.13.8145. PMID\u00a09079628.Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). “Construction and characterization of a full length-enriched and a 5′-end-enriched cDNA library”. Gene. 200 (1\u20132): 149\u201356. doi:10.1016\/S0378-1119(97)00411-3. PMID\u00a09373149.Madani N, Kabat D (Dec 1998). “An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein”. Journal of Virology. 72 (12): 10251\u20135. doi:10.1128\/JVI.72.12.10251-10255.1998. PMC\u00a0110608. PMID\u00a09811770.Simon JH, Gaddis NC, Fouchier RA, Malim MH (Dec 1998). “Evidence for a newly discovered cellular anti-HIV-1 phenotype”. Nature Medicine. 4 (12): 1397\u2013400. doi:10.1038\/3987. PMID\u00a09846577. S2CID\u00a025235070.Mulder LC, Muesing MA (Sep 2000). “Degradation of HIV-1 integrase by the N-end rule pathway”. The Journal of Biological Chemistry. 275 (38): 29749\u201353. doi:10.1074\/jbc.M004670200. PMID\u00a010893419.Sheehy AM, Gaddis NC, Choi JD, Malim MH (Aug 2002). “Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein”. Nature. 418 (6898): 646\u201350. Bibcode:2002Natur.418..646S. doi:10.1038\/nature00939. PMID\u00a012167863. S2CID\u00a04403228.Huang X, Seifert U, Salzmann U, Henklein P, Preissner R, Henke W, Sijts AJ, Kloetzel PM, Dubiel W (Nov 2002). “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 of Molecular Biology. 323 (4): 771\u201382. doi:10.1016\/S0022-2836(02)00998-1. PMID\u00a012419264.Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). “Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides”. Nature Biotechnology. 21 (5): 566\u20139. doi:10.1038\/nbt810. PMID\u00a012665801. S2CID\u00a023783563.Gaddis NC, Chertova E, Sheehy AM, Henderson LE, Malim MH (May 2003). “Comprehensive investigation of the molecular defect in vif-deficient human immunodeficiency virus type 1 virions”. Journal of Virology. 77 (10): 5810\u201320. doi:10.1128\/JVI.77.10.5810-5820.2003. PMC\u00a0154025. PMID\u00a012719574.Lecossier D, Bouchonnet F, Clavel F, Hance AJ (May 2003). “Hypermutation of HIV-1 DNA in the absence of the Vif protein”. Science. 300 (5622): 1112. doi:10.1126\/science.1083338. PMID\u00a012750511. S2CID\u00a020591673.Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L (Jul 2003). “The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA”. Nature. 424 (6944): 94\u20138. Bibcode:2003Natur.424…94Z. doi:10.1038\/nature01707. PMC\u00a01350966. PMID\u00a012808465.Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D (Jul 2003). “Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts”. Nature. 424 (6944): 99\u2013103. Bibcode:2003Natur.424…99M. doi:10.1038\/nature01709. PMID\u00a012808466. S2CID\u00a04347374.Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim MH (Jun 2003). “DNA deamination mediates innate immunity to retroviral infection”. Cell. 113 (6): 803\u20139. doi:10.1016\/S0092-8674(03)00423-9. PMID\u00a012809610. S2CID\u00a0544971.  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