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Gene Review

PSMC5  -  proteasome (prosome, macropain) 26S...

Homo sapiens

Synonyms: 26S protease regulatory subunit 8, 26S proteasome AAA-ATPase subunit RPT6, Proteasome 26S subunit ATPase 5, Proteasome subunit p45, S8, ...
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Disease relevance of PSMC5


High impact information on PSMC5


Chemical compound and disease context of PSMC5


Biological context of PSMC5

  • MIP224 also interacts in yeast with other CAD proteins, including MSS1, which is proteasomal, and TRIP1, which is associated with transcriptional activation [10].
  • After 4 h of labeling, the endocrine cells exhibited a sevenfold higher phosphorylation of p42 than the duct cells, whereas p45 was phosphorylated only in endocrine cells [11].
  • Furthermore, proteasome dysfunction by a proteasome inhibitor or siRNA-mediated knock-down of Sug1 caused the up-regulation of MYO18B protein and MYO18B was polyubiquitinated in vivo [12].
  • Inhibition of TRIP1/S8/hSug1, a component of the human 19S proteasome, enhances mitotic apoptosis induced by spindle poisons [13].
  • These results indicate that inhibition of TRIP1/S8/hSug1 function by expression of a truncated version of the protein or by siRNA-mediated suppression enhances cell death in response to spindle poison treatment [13].

Anatomical context of PSMC5

  • Furthermore, overexpression of SUG1 in normal fibroblasts induced arrest of transcription and a chromatin collapse in vivo [14].
  • After isolation and culture, both duct and islet cell preparations contained the Ipf-1 immunoreactive proteins p42 and p45 (42 and 45 kDa, respectively) in similar proportions, but the expression levels were twofold lower in duct cells [11].
  • Stable expression of the truncated TRIP1/S8/hSug1 in HeLa cells [OP-TRIP1(88-406)] resulted in a decrease of measurable cellular proteasome activity, indicating that OP-TRIP1(88-406) had a dominant-negative effect on proteasome function [13].
  • Both membrane (p55) and soluble (p45) forms of TAC-reactive interleukin-2 receptor (IL-2R) are expressed and/or released by activated lymphocytes or monocytes [15].
  • These data suggest that Jak-2 kinase and an activated isoform of MAP kinase, p45, are detected following incubation with IL-5, and may mediate some of this cytokine's effects on eosinophils in a manner unique to the activation pathways previously described for other cells [16].

Associations of PSMC5 with chemical compounds

  • One of these, the protein of approximately 45 kDa (p45), was tyrosine phosphorylated following treatment of eosinophils with IL-5 and PMA, as seen by anti-phosphotyrosine immunoprecipitation and immunoblotting with anti-MAP kinase Abs [16].
  • This new more active ICE form serves both as an intermediate enzyme to cleave p45 as well as a substrate for the formation of the final active ICE (ED50 of 1 nM L-742,395 labeling of p20 and for p22, an NH2-terminally extended form of p20) [17].
  • Using Northern analysis, we observed no significant difference between the amount of either TIF-1 or SUG-1 mRNA expressed in parental MCF-7 and MCF-7 tamoxifen-resistant cell lines [5].
  • The SH-reagent N-ethylmaleimide prevented p45 labeling, unless T3 was present to protect the T3 transport activity and the high affinity T3-binding sites from inactivation [18].
  • [Gavva, N. R., Gavva, R., Ermekova, K., Sudol, M., and Shen, J. C. (1997) J. Biol. Chem. 272, 24105-24108] reported that human p45 contains a PPXY motif that binds WW domains [19].

Physical interactions of PSMC5

  • MYO18B interacts with the proteasomal subunit Sug1 and is degraded by the ubiquitin-proteasome pathway [12].
  • Mutations and alterations of the IGF-axis as well as of chromosome 1p34, where the genes for histone deacetylase 1 (HDAC1) and transforming growth factor beta receptor interacting protein-1 (TRIP-1) map, are frequent events in hepatocarcinogenesis [20].

Regulatory relationships of PSMC5

  • Functionally, the overexpression of SUG1 inhibited both ERalpha- and ERbeta-mediated transcription in the presence of ligands [21].

Other interactions of PSMC5

  • Specifically, in vitro and in vivo co-precipitation studies have revealed that the 19S regulatory components of the proteasome, Sug1 (S8) and S4, bind through amino acids (aa) 4-25 of Ad5 E1A [22].
  • The association of MYO18B with Sug1 was further confirmed by GST pull-down, co-immunoprecipitation, and immunocytochemistry [12].
  • These findings indicate that the ubiquitin/proteasome-mediated degradation of both ER proteins may involve the interaction of SUG1 with both ERs [21].
  • On the other hand, bisphenol A (BSA), which activated ER-mediated transcription, did not enhance the interaction between ERbeta and SUG1 [21].
  • Previously we demonstrated that the interaction between the suppressor for Gal 1 (SUG1) and nuclear receptors, the vitamin D receptor, or the pregnane X receptor was involved in proteasome-mediated degradation [21].

Analytical, diagnostic and therapeutic context of PSMC5

  • (iii) In fibroblasts under non-overexpression conditions a portion of SUG1 is bound to the TFIIH holocomplex as deduced from co-purification, immunopurification and nickel-chelate affinity chromatography using functional tagged TFIIH [14].
  • (i) SUG1 interacts with XPB but not with the other core TFIIH subunits in the two-hybrid assay [14].
  • Small interfering RNA (siRNA)-mediated knockdown of TRIP1/S8/hSug1 resulted in a reduction of general proteasome activity and an increase in mitotic index [13].
  • Chromatin immunoprecipitation reveals that E1A, S8 and the 20S proteasome are recruited to both Ad early region gene promoters and early region gene sequences during Ad infection, suggesting their requirement in both transcriptional initiation and elongation [23].
  • DNA and RNA microinjections in Xenopus oocytes have shown that U17XS8 RNA is not the product of an independent transcription unit, but is produced by processing of intron sequences of r-protein S8 transcript, as has been recently shown for other small nucleolar RNAs encoded in the introns of other genes [24].


  1. Alterations in a yeast protein resembling HIV Tat-binding protein relieve requirement for an acidic activation domain in GAL4. Swaffield, J.C., Bromberg, J.F., Johnston, S.A. Nature (1992) [Pubmed]
  2. cDNA cloning of a new putative ATPase subunit p45 of the human 26S proteasome, a homolog of yeast transcriptional factor Sug1p. Akiyama, K., Yokota, K., Kagawa, S., Shimbara, N., DeMartino, G.N., Slaughter, C.A., Noda, C., Tanaka, K. FEBS Lett. (1995) [Pubmed]
  3. An increase in cytoplasmic CTP accelerates the reaction catalyzed by CTP:phosphocholine cytidylyltransferase in poliovirus-infected HeLa cells. Choy, P.C., Paddon, H.B., Vance, D.E. J. Biol. Chem. (1980) [Pubmed]
  4. Regions of prostate-specific antigen (PSA) promoter confer androgen-independent expression of PSA in prostate cancer cells. Yeung, F., Li, X., Ellett, J., Trapman, J., Kao, C., Chung, L.W. J. Biol. Chem. (2000) [Pubmed]
  5. Expression of nuclear receptor interacting proteins TIF-1, SUG-1, receptor interacting protein 140, and corepressor SMRT in tamoxifen-resistant breast cancer. Chan, C.M., Lykkesfeldt, A.E., Parker, M.G., Dowsett, M. Clin. Cancer Res. (1999) [Pubmed]
  6. Interaction of thyroid-hormone receptor with a conserved transcriptional mediator. Lee, J.W., Ryan, F., Swaffield, J.C., Johnston, S.A., Moore, D.D. Nature (1995) [Pubmed]
  7. Heregulin induces tyrosine phosphorylation of HER4/p180erbB4. Plowman, G.D., Green, J.M., Culouscou, J.M., Carlton, G.W., Rothwell, V.M., Buckley, S. Nature (1993) [Pubmed]
  8. Phosphorylation by p38MAPK and recruitment of SUG-1 are required for RA-induced RAR gamma degradation and transactivation. Giannì, M., Bauer, A., Garattini, E., Chambon, P., Rochette-Egly, C. EMBO J. (2002) [Pubmed]
  9. Differential effects of retinoic acid isomers on the expression of nuclear receptor co-regulators in neuroblastoma. Lovat, P.E., Annicchiarico-Petruzzelli, M., Corazzari, M., Dobson, M.G., Malcolm, A.J., Pearson, A.D., Melino, G., Redfern, C.P. FEBS Lett. (1999) [Pubmed]
  10. A component of the 26S proteasome binds on orphan member of the nuclear hormone receptor superfamily. Choi, H.S., Seol, W., Moore, D.D. J. Steroid Biochem. Mol. Biol. (1996) [Pubmed]
  11. Adult human pancreatic duct and islet cells exhibit similarities in expression and differences in phosphorylation and complex formation of the homeodomain protein Ipf-1. Heimberg, H., Bouwens, L., Heremans, Y., Van De Casteele, M., Lefebvre, V., Pipeleers, D. Diabetes (2000) [Pubmed]
  12. MYO18B interacts with the proteasomal subunit Sug1 and is degraded by the ubiquitin-proteasome pathway. Inoue, T., Kon, T., Ajima, R., Ohkura, R., Tani, M., Yokota, J., Sutoh, K. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  13. Inhibition of TRIP1/S8/hSug1, a component of the human 19S proteasome, enhances mitotic apoptosis induced by spindle poisons. Yamada, H.Y., Gorbsky, G.J. Mol. Cancer Ther. (2006) [Pubmed]
  14. The XPB subunit of repair/transcription factor TFIIH directly interacts with SUG1, a subunit of the 26S proteasome and putative transcription factor. Weeda, G., Rossignol, M., Fraser, R.A., Winkler, G.S., Vermeulen, W., van 't Veer, L.J., Ma, L., Hoeijmakers, J.H., Egly, J.M. Nucleic Acids Res. (1997) [Pubmed]
  15. The malignant B cells from B-chronic lymphocytic leukemia patients release TAC-soluble interleukin-2 receptors. Kay, N.E., Burton, J., Wagner, D., Nelson, D.L. Blood (1988) [Pubmed]
  16. IL-5 activates a 45-kilodalton mitogen-activated protein (MAP) kinase and Jak-2 tyrosine kinase in human eosinophils. Bates, M.E., Bertics, P.J., Busse, W.W. J. Immunol. (1996) [Pubmed]
  17. Activation of the native 45-kDa precursor form of interleukin-1-converting enzyme. Yamin, T.T., Ayala, J.M., Miller, D.K. J. Biol. Chem. (1996) [Pubmed]
  18. Identification by photoaffinity labeling of a membrane thyroid hormone-binding protein associated with the triiodothyronine transport system in rat erythrocytes. Samson, M., Osty, J., Blondeau, J.P. Endocrinology (1993) [Pubmed]
  19. Physical and functional interactions between the transactivation domain of the hematopoietic transcription factor NF-E2 and WW domains. Mosser, E.A., Kasanov, J.D., Forsberg, E.C., Kay, B.K., Ney, P.A., Bresnick, E.H. Biochemistry (1998) [Pubmed]
  20. Modulating IGFBP-3 expression by trichostatin A: potential therapeutic role in the treatment of hepatocellular carcinoma. Gray, S.G., Kytola, S., Lui, W.O., Larsson, C., Ekstrom, T.J. Int. J. Mol. Med. (2000) [Pubmed]
  21. Involvement of suppressor for Gal 1 in the ubiquitin/proteasome-mediated degradation of estrogen receptors. Masuyama, H., Hiramatsu, Y. J. Biol. Chem. (2004) [Pubmed]
  22. Regulation of the 26S proteasome by adenovirus E1A. Turnell, A.S., Grand, R.J., Gorbea, C., Zhang, X., Wang, W., Mymryk, J.S., Gallimore, P.H. EMBO J. (2000) [Pubmed]
  23. Roles for APIS and the 20S proteasome in adenovirus E1A-dependent transcription. Rasti, M., Grand, R.J., Yousef, A.F., Shuen, M., Mymryk, J.S., Gallimore, P.H., Turnell, A.S. EMBO J. (2006) [Pubmed]
  24. U17XS8, a small nucleolar RNA with a 12 nt complementarity to 18S rRNA and coded by a sequence repeated in the six introns of Xenopus laevis ribosomal protein S8 gene. Cecconi, F., Mariottini, P., Loreni, F., Pierandrei-Amaldi, P., Campioni, N., Amaldi, F. Nucleic Acids Res. (1994) [Pubmed]
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