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Gene Review

PSME1  -  proteasome (prosome, macropain) activator...

Homo sapiens

Synonyms: 11S regulator complex subunit alpha, Activator of multicatalytic protease subunit 1, IFI5111, IGUP I-5111, Interferon gamma up-regulated I-5111 protein, ...
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Disease relevance of PSME1


High impact information on PSME1

  • Whereas REGalpha activates proteasomal hydrolysis of peptides with hydrophobic, acidic or basic residues in the P1 position, REGgamma only activates cleavage after basic residues [6].
  • Five REGalpha mutants that remain inactive in the mixing assay contain amino acid substitutions clustered between Arg-141 and Gly-149 [7].
  • Combining PCR mutagenesis with an in vitro activity assay, we have isolated and characterized 36 inactive, single-site mutants of recombinant REGalpha [7].
  • In contrast to such extreme deficiencies, we found unaltered or only partially decreased expression of PA28alpha and PA28beta in tumor cell lines [8].
  • In this study, we describe the complete nucleotide sequences of the mouse genes, Psme1, Psme2, and Psme3, coding for the alpha-, beta-, and gamma-subunits, respectively [9].

Chemical compound and disease context of PSME1


Biological context of PSME1


Anatomical context of PSME1


Associations of PSME1 with chemical compounds

  • Proteasome activator subunit PA28 alpha and related Ki antigen (PA28 gamma) are absent from the nuclear fraction purified by sucrose gradient centrifugation [18].
  • IGUP I-5111 contains the RGD sequence found in many extracellular glycoprotein ligands of the integrin receptor family and it is found at least partially in the culture supernatant [3].
  • The Psme1 and Psme2 genes are located approximately 6 kb apart with their 3'-ends pointing toward each other on bands C2 to D1 of mouse chromosome 14, supporting the idea that they emerged by tandem duplication [9].
  • PSME-enhanced expression is repressed in the presence of androgen, mimicking the repression of the endogenous FOLH1 gene [19].

Physical interactions of PSME1

  • Each subunit is capable of activating the proteasome, and when combined, they form superactive REGalpha/REGbeta complexes [20].

Regulatory relationships of PSME1

  • Recombinant alpha and beta subunits bind each other with high affinity, and the REGalpha/beta heteromeric complex activates hydrolysis of LLVY-methylcoumaryl-7-amide (LLVY-MCA) and LLE-beta-nitroanilide (LLE-betaNA) more than REGalpha or REGbeta alone [2].

Other interactions of PSME1

  • At the transcript level, the interferon-gamma-responsive subunits LMP2 (beta1i), MECL1 (beta2i), and the proteasome activator subunit PA28alpha were markedly up regulated [21].
  • Finally we showed that the human chromosomal genes of PA28 alpha and PA28 gamma were located on 14q11.2 and 17q21.32-21.33, respectively [22].
  • Likewise, the expression of the IFN-gamma-inducible proteasome regulator PA28 alpha beta was also impaired in MCMV-infected cells [23].
  • Further, HSC5 and HSC7 show diminished expression of LMP7/tapasin, and PA28alpha/beta, respectively [24].
  • METHODS: Serum samples were obtained from 219 patients with various connective tissue diseases. cDNA encoding full-length human PA28alpha and Ki were produced by polymerase chain reaction [4].

Analytical, diagnostic and therapeutic context of PSME1


  1. 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. Huang, X., Seifert, U., Salzmann, U., Henklein, P., Preissner, R., Henke, W., Sijts, A.J., Kloetzel, P.M., Dubiel, W. J. Mol. Biol. (2002) [Pubmed]
  2. Characterization of recombinant REGalpha, REGbeta, and REGgamma proteasome activators. Realini, C., Jensen, C.C., Zhang, Z., Johnston, S.C., Knowlton, J.R., Hill, C.P., Rechsteiner, M. J. Biol. Chem. (1997) [Pubmed]
  3. Interferon-gamma up-regulates a unique set of proteins in human keratinocytes. Molecular cloning and expression of the cDNA encoding the RGD-sequence-containing protein IGUP I-5111. Honoré, B., Leffers, H., Madsen, P., Celis, J.E. Eur. J. Biochem. (1993) [Pubmed]
  4. Autoimmune response to proteasome activator 28alpha in patients with connective tissue diseases. Matsushita, M., Takasaki, Y., Takeuchi, K., Yamada, H., Matsudaira, R., Hashimoto, H. J. Rheumatol. (2004) [Pubmed]
  5. Targeting prostate cancer with conditionally replicative adenovirus using PSMA enhancer. Lee, S.J., Zhang, Y., Lee, S.D., Jung, C., Li, X., Kim, H.S., Bae, K.H., Jeng, M.H., Kao, C., Gardner, T. Mol. Ther. (2004) [Pubmed]
  6. Lysine 188 substitutions convert the pattern of proteasome activation by REGgamma to that of REGs alpha and beta. Li, J., Gao, X., Ortega, J., Nazif, T., Joss, L., Bogyo, M., Steven, A.C., Rechsteiner, M. EMBO J. (2001) [Pubmed]
  7. Identification of an activation region in the proteasome activator REGalpha. Zhang, Z., Clawson, A., Realini, C., Jensen, C.C., Knowlton, J.R., Hill, C.P., Rechsteiner, M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  8. Down-regulation of the transporter for antigen presentation, proteasome subunits, and class I major histocompatibility complex in tumor cell lines. Johnsen, A., France, J., Sy, M.S., Harding, C.V. Cancer Res. (1998) [Pubmed]
  9. Characterization of the mouse PA28 activator complex gene family: complete organizations of the three member genes and a physical map of the approximately 150-kb region containing the alpha- and beta-subunit genes. Kohda, K., Ishibashi, T., Shimbara, N., Tanaka, K., Matsuda, Y., Kasahara, M. J. Immunol. (1998) [Pubmed]
  10. NFATc1 with AP-3 site binding specificity mediates gene expression of prostate-specific-membrane-antigen. Lee, S.J., Lee, K., Yang, X., Jung, C., Gardner, T., Kim, H.S., Jeng, M.H., Kao, C. J. Mol. Biol. (2003) [Pubmed]
  11. Isolation of genes differentially expressed at the downstream anastomosis of prosthetic arterial grafts with use of mRNA differential display. Hamdan, A.D., Aiello, L.P., Quist, W.C., Ozaki, C.K., Contreras, M.A., Phaneuf, M.D., Ruiz, C., King, G.L., LoGerfo, F.W. J. Vasc. Surg. (1995) [Pubmed]
  12. Organization of the genes encoding the human proteasome activators PA28alpha and beta. McCusker, D., Wilson, M., Trowsdale, J. Immunogenetics (1999) [Pubmed]
  13. Structural plasticity of the proteasome and its function in antigen processing. Groettrup, M., van den Broek, M., Schwarz, K., Macagno, A., Khan, S., de Giuli, R., Schmidtke, G. Crit. Rev. Immunol. (2001) [Pubmed]
  14. The proteasome activator 11 S REG or PA28: chimeras implicate carboxyl-terminal sequences in oligomerization and proteasome binding but not in the activation of specific proteasome catalytic subunits. Li, J., Gao, X., Joss, L., Rechsteiner, M. J. Mol. Biol. (2000) [Pubmed]
  15. Pronounced up-regulation of the PA28alpha/beta proteasome regulator but little increase in the steady-state content of immunoproteasome during dendritic cell maturation. Macagno, A., Kuehn, L., de Giuli, R., Groettrup, M. Eur. J. Immunol. (2001) [Pubmed]
  16. The proteasome 11S regulator subunit REG alpha (PA28 alpha) is a heptamer. Johnston, S.C., Whitby, F.G., Realini, C., Rechsteiner, M., Hill, C.P. Protein Sci. (1997) [Pubmed]
  17. Rapamycin inhibits proteasome activator expression and proteasome activity. Wang, X., Omura, S., Szweda, L.I., Yang, Y., Bérard, J., Seminaro, J., Wu, J. Eur. J. Immunol. (1997) [Pubmed]
  18. Proteasome activator subunit PA28 alpha and related Ki antigen (PA28 gamma) are absent from the nuclear fraction purified by sucrose gradient centrifugation. Wójcik, C. Int. J. Biochem. Cell Biol. (1999) [Pubmed]
  19. A tissue-specific enhancer of the prostate-specific membrane antigen gene, FOLH1. Watt, F., Martorana, A., Brookes, D.E., Ho, T., Kingsley, E., O'Keefe, D.S., Russell, P.J., Heston, W.D., Molloy, P.L. Genomics (2001) [Pubmed]
  20. The proteasome activator 11 S regulator or PA28. Contribution By both alpha and beta subunits to proteasome activation. Zhang, Z., Clawson, A., Rechsteiner, M. J. Biol. Chem. (1998) [Pubmed]
  21. Immunoproteasome subunit LMP2 expression is deregulated in Sjogren's syndrome but not in other autoimmune disorders. Krause, S., Kuckelkorn, U., Dörner, T., Burmester, G.R., Feist, E., Kloetzel, P.M. Ann. Rheum. Dis. (2006) [Pubmed]
  22. Molecular properties of the proteasome activator PA28 family proteins and gamma-interferon regulation. Tanahashi, N., Yokota, K., Ahn, J.Y., Chung, C.H., Fujiwara, T., Takahashi, E., DeMartino, G.N., Slaughter, C.A., Toyonaga, T., Yamamura, K., Shimbara, N., Tanaka, K. Genes Cells (1997) [Pubmed]
  23. A cytomegalovirus inhibitor of gamma interferon signaling controls immunoproteasome induction. Khan, S., Zimmermann, A., Basler, M., Groettrup, M., Hengel, H. J. Virol. (2004) [Pubmed]
  24. High expression of HLA-A2 on an oral squamous cell carcinoma with down-regulated transporter for antigen presentation. Matsui, M., Ikeda , M., Akatsuka, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
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