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PSMA7

From Wikipedia, the free encyclopedia
PSMA7
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPSMA7, C6, HSPC, RC6-1, XAPC7, HEL-S-276, proteasome subunit alpha 7, proteasome 20S subunit alpha 7
External IDsOMIM: 606607; MGI: 1347070; HomoloGene: 105299; GeneCards: PSMA7; OMA:PSMA7 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5688

26444

Ensembl

ENSG00000101182

ENSMUSG00000027566

UniProt

O14818

Q9Z2U0

RefSeq (mRNA)

NM_152255
NM_002792

NM_001289476
NM_011969

RefSeq (protein)

NP_002783

NP_001276405
NP_036099

Location (UCSC)Chr 20: 62.14 – 62.14 MbChr 2: 179.68 – 179.68 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Proteasome subunit alpha type-7 also known as 20S proteasome subunit alpha-4 is a protein that in humans is encoded by the PSMA7 gene.[5][6] This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.

Function

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The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. As a component of alpha ring, proteasome subunit alpha type-7 contributes to the formation of heptameric alpha rings and substrate entrance gate. Importantly, this subunit plays a critical role in the assembly of 19S base and 20S. This particular subunit has been shown to interact specifically with the hepatitis B virus X protein, a protein critical to viral replication. In addition, this subunit is involved in regulating hepatitis virus C internal ribosome entry site (IRES) activity, an activity essential for viral replication. This core alpha subunit is also involved in regulating the hypoxia-inducible factor-1alpha, a transcription factor important for cellular responses to oxygen tension. Recent study on underlying mechanisms of E3 ligase Parkin-related neurodegeneration identified this proteasome subunit as one of Parkin associating partner. The protein-protein interaction was initiated between the C-terminal domain of Parkin and C-terminal of subunit alpha4 (systematic nomenclature).[7]

Structure

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Expression

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The gene PSMA7 encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. This gene has 7 exons and locates at a chromosome band 20q13.33. Multiple isoforms of this subunit arising from alternative splicing may exist but alternative transcripts for only two isoforms have been defined. A pseudogene has been identified on chromosome 9.[6]

The human protein Proteasome subunit alpha type-7 is 28 kDa in size and composed of 248 amino acids. The calculated theoretical pI (Isoelectric point) of this protein is 8.60.

Complex assembly

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The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each formed by 7 alpha subunits, and the two central rings are each formed by 7 beta subunits. Three beta subunits (beta1, beta2, and beta5) each contains a proteolytic active site and has distinct substrate preferences. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway.[8][9]

Mechanism

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Crystal structures of isolated 20S proteasome complex demonstrate that the two rings of beta subunits form a proteolytic chamber and maintain all their active sites of proteolysis within the chamber.[9] Concomitantly, the rings of alpha subunits form the entrance for substrates entering the proteolytic chamber. In an inactivated 20S proteasome complex, the gate into the internal proteolytic chamber are guarded by the N-terminal tails of specific alpha-subunit.[10][11] The proteolytic capacity of 20S core particle (CP) can be activated when CP associates with one or two regulatory particles (RP) on one or both side of alpha rings. These regulatory particles include 19S proteasome complexes, 11S proteasome complex, etc. Following the CP-RP association, the confirmation of certain alpha subunits will change and consequently cause the opening of substrate entrance gate. Besides RPs, the 20S proteasomes can also be effectively activated by other mild chemical treatments, such as exposure to low levels of sodium dodecylsulfate (SDS) or NP-14.[11][12]

Clinical significance

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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.

The proteasomes form a pivotal component for the ubiquitin–proteasome system (UPS) [13] 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.[14] 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,[15][16] cardiovascular diseases,[17][18][19] inflammatory responses and autoimmune diseases,[20] and systemic DNA damage responses leading to malignancies.[21]

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,[22] Parkinson's disease[23] and Pick's disease,[24] Amyotrophic lateral sclerosis (ALS),[24] Huntington's disease,[23] Creutzfeldt–Jakob disease,[25] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[26] and several rare forms of neurodegenerative diseases associated with dementia.[27] As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury,[28] ventricular hypertrophy[29] and heart failure.[30] 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.[31] 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).[20] 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.[32] Lastly, autoimmune disease patients with SLE, Sjögren syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[33]

Reports have shown that the proteasome subunit alpha type-7 (PSMA7) is overexpressed in colorectal cancer and associated with its hepatic metastasis.[34][35] It was further reported that PSMA7 is associated with nucleotide-binding oligomerization domain-containing protein 1 (NOD1) as a negative regulator and may promote tumor growth by its inhibitory role on NOD1.[36]

Interactions

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PSMA7 has been shown to interact with HIF1A[37] and PLK1.[38]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000101182 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027566 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Huang J, Kwong J, Sun EC, Liang TJ (August 1996). "Proteasome complex as a potential cellular target of hepatitis B virus X protein". Journal of Virology. 70 (8): 5582–91. doi:10.1128/JVI.70.8.5582-5591.1996. PMC 190518. PMID 8764072.
  6. ^ a b "Entrez Gene: PSMA7 proteasome (prosome, macropain) subunit, alpha type, 7".
  7. ^ Dächsel JC, Lücking CB, Deeg S, Schultz E, Lalowski M, Casademunt E, Corti O, Hampe C, Patenge N, Vaupel K, Yamamoto A, Dichgans M, Brice A, Wanker EE, Kahle PJ, Gasser T (July 2005). "Parkin interacts with the proteasome subunit alpha4". FEBS Letters. 579 (18): 3913–9. doi:10.1016/j.febslet.2005.06.003. PMID 15987638. S2CID 84582722.
  8. ^ Coux O, Tanaka K, Goldberg AL (1996). "Structure and functions of the 20S and 26S proteasomes". Annual Review of Biochemistry. 65: 801–47. doi:10.1146/annurev.bi.65.070196.004101. PMID 8811196.
  9. ^ a b Tomko RJ, Hochstrasser M (2013). "Molecular architecture and assembly of the eukaryotic proteasome". Annual Review of Biochemistry. 82: 415–45. doi:10.1146/annurev-biochem-060410-150257. PMC 3827779. PMID 23495936.
  10. ^ Groll M, Ditzel L, Löwe J, Stock D, Bochtler M, Bartunik HD, Huber R (April 1997). "Structure of 20S proteasome from yeast at 2.4 A resolution". Nature. 386 (6624): 463–71. Bibcode:1997Natur.386..463G. doi:10.1038/386463a0. PMID 9087403. S2CID 4261663.
  11. ^ a b Groll M, Bajorek M, Köhler A, Moroder L, Rubin DM, Huber R, Glickman MH, Finley D (November 2000). "A gated channel into the proteasome core particle". Nature Structural Biology. 7 (11): 1062–7. doi:10.1038/80992. PMID 11062564. S2CID 27481109.
  12. ^ Zong C, Gomes AV, Drews O, Li X, Young GW, Berhane B, Qiao X, French SW, Bardag-Gorce F, Ping P (August 2006). "Regulation of murine cardiac 20S proteasomes: role of associating partners". Circulation Research. 99 (4): 372–80. doi:10.1161/01.RES.0000237389.40000.02. PMID 16857963.
  13. ^ Kleiger G, Mayor T (June 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.
  14. ^ Goldberg AL, Stein R, Adams J (August 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.
  15. ^ Sulistio YA, Heese K (March 2016). "The Ubiquitin–Proteasome System and Molecular Chaperone Deregulation in Alzheimer's Disease". Molecular Neurobiology. 53 (2): 905–31. doi:10.1007/s12035-014-9063-4. PMID 25561438. S2CID 14103185.
  16. ^ 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.
  17. ^ Sandri M, Robbins J (June 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.
  18. ^ Drews O, Taegtmeyer H (December 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.
  19. ^ Wang ZV, Hill JA (February 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.
  20. ^ a b Karin M, Delhase M (February 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.
  21. ^ Ermolaeva MA, Dakhovnik A, Schumacher B (September 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.
  22. ^ Checler F, da Costa CA, Ancolio K, Chevallier N, Lopez-Perez E, Marambaud P (July 2000). "Role of the proteasome in Alzheimer's disease". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1502 (1): 133–8. doi:10.1016/s0925-4439(00)00039-9. PMID 10899438.
  23. ^ a b Chung KK, Dawson VL, Dawson TM (November 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. S2CID 2211658.
  24. ^ a b Ikeda K, Akiyama H, Arai T, Ueno H, Tsuchiya K, Kosaka K (July 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. S2CID 22396490.
  25. ^ 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. S2CID 28190967.
  26. ^ Mathews KD, Moore SA (January 2003). "Limb-girdle muscular dystrophy". Current Neurology and Neuroscience Reports. 3 (1): 78–85. doi:10.1007/s11910-003-0042-9. PMID 12507416. S2CID 5780576.
  27. ^ Mayer RJ (March 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.
  28. ^ Calise J, Powell SR (February 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.
  29. ^ Predmore JM, Wang P, Davis F, Bartolone S, Westfall MV, Dyke DB, Pagani F, Powell SR, Day SM (March 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.
  30. ^ Powell SR (July 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. S2CID 7073263.
  31. ^ Adams J (April 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.
  32. ^ Ben-Neriah Y (January 2002). "Regulatory functions of ubiquitination in the immune system". Nature Immunology. 3 (1): 20–6. doi:10.1038/ni0102-20. PMID 11753406. S2CID 26973319.
  33. ^ Egerer K, Kuckelkorn U, Rudolph PE, Rückert JC, Dörner T, Burmester GR, Kloetzel PM, Feist E (October 2002). "Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseases". The Journal of Rheumatology. 29 (10): 2045–52. PMID 12375310.
  34. ^ Hu XT, Chen W, Wang D, Shi QL, Zhang FB, Liao YQ, Jin M, He C (February 2008). "The proteasome subunit PSMA7 located on the 20q13 amplicon is overexpressed and associated with liver metastasis in colorectal cancer". Oncology Reports. 19 (2): 441–6. doi:10.3892/or.19.2.441. PMID 18202793.
  35. ^ Hu XT, Chen W, Zhang FB, Shi QL, Hu JB, Geng SM, He C (November 2009). "Depletion of the proteasome subunit PSMA7 inhibits colorectal cancer cell tumorigenicity and migration". Oncology Reports. 22 (5): 1247–52. doi:10.3892/or_00000561. PMID 19787246.
  36. ^ Yang L, Tang Z, Zhang H, Kou W, Lu Z, Li X, Li Q, Miao Z (2013). "PSMA7 directly interacts with NOD1 and regulates its function". Cellular Physiology and Biochemistry. 31 (6): 952–9. doi:10.1159/000350113. PMID 23839082.
  37. ^ Cho S, Choi YJ, Kim JM, Jeong ST, Kim JH, Kim SH, Ryu SE (June 2001). "Binding and regulation of HIF-1alpha by a subunit of the proteasome complex, PSMA7". FEBS Letters. 498 (1): 62–6. doi:10.1016/S0014-5793(01)02499-1. PMID 11389899. S2CID 83756271.
  38. ^ Feng Y, Longo DL, Ferris DK (January 2001). "Polo-like kinase interacts with proteasomes and regulates their activity". Cell Growth & Differentiation. 12 (1): 29–37. PMID 11205743.

Further reading

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