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Gene Review

PSMD10  -  proteasome (prosome, macropain) 26S...

Homo sapiens

Synonyms: 26S proteasome non-ATPase regulatory subunit 10, 26S proteasome regulatory subunit p28, Gankyrin, dJ889N15.2, p28, ...
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Disease relevance of PSMD10

  • Gankyrin is an ankyrin repeat oncoprotein commonly overexpressed in hepatocellular carcinomas [1].
  • Previous studies identified gankyrin as a component of the 26S proteasome that is consistently overexpressed in liver cancer and promotes cell transformation by binding RB [2].
  • Transduction with a HIV Tat-MAGE-A4DeltaN1 fusion protein suppressed anchorage-independent growth of gankyrin-overexpressing cells in vitro and in vivo [3].
  • The newly discovered oncogenic protein gankyrin, which contains six ankyrin repeats, has been reported to be involved in the phosphorylation and degradation of the retinoblastoma gene product, Rb [4].
  • We conclude that: 1) EIA testing and WB/RIPA verification identified 10 (0.025%) HTLV-1 infected individuals among 39,898 low-risk blood donors; 2) anti-p24 may be a more sensitive and specific indicator of HTLV-1 infection than antibodies to p19, p28, or p53/55; and 3) presently, both WB and RIPA are needed to verify HTLV-1 EIA reactivity [5].

High impact information on PSMD10

  • The expression of gankyrin was increased in all 34 hepatocellular carcinomas studied [6].
  • These results demonstrate the importance of ubiquitin-proteasome pathway in the regulation of cell growth and oncogenic transformation, and indicate that gankyrin overexpression contributes to hepatocarcinogenesis by destabilizing RB1 [6].
  • Gankyrin induced anchorage-independent growth and tumorigenicity in NIH/3T3 cells [6].
  • Here, we discuss the activities of gankyrin and present a model for its function in the regulation of pRb and p53 [7].
  • In conclusion, gankyrin is a small versatile cell cycle regulator that illustrates the essential interplay between the ubiquitin proteasome system and gene expression in the cell [7].

Chemical compound and disease context of PSMD10


Biological context of PSMD10


Anatomical context of PSMD10


Associations of PSMD10 with chemical compounds

  • The phosphokinase activity of p28 was specific to the serine residue but was not to the tyrosine residue [12].
  • Gankyrin has been crystallized from polyethylene glycol solutions and diffraction data have been obtained from these crystals that extend to 2.1 A spacing [15].
  • The isozyme form of eukaryotic initiation factor 4F [eIF-(iso)4F] from wheat germ is composed of a p28 subunit that binds the 7-methylguanine cap of mRNA and a p86 subunit having unknown function [16].
  • Gel filtration column chromatography of unreduced p28 in the presence of 0.5% NP-40 or 0.1% deoxycholate gave elution characteristics consistent with a m.w. of approximately 60,000 to 100,000 [17].
  • Protein p28 was prominently represented in plasma membranes isolated on discontinuous sucrose density gradients and was identified as a cell surface glycoprotein based on studies in which intact stimulated cells were exposed to degradative enzymes [18].

Physical interactions of PSMD10

  • In the current issue of Cancer Cell, Fujita and colleagues (Higashitsuji et al., 2005) show that gankyrin also binds MDM2 and facilitates its destruction of p53 [2].

Regulatory relationships of PSMD10

  • The proteasomal ATPases are part of the AAA (ATPases associated with diverse cellular activities) family, members of which are molecular chaperones; gankyrin complexes may therefore influence CDK4 function during oncogenesis [10].
  • The oncoprotein gankyrin negatively regulates both p53 and RB by enhancing proteasomal degradation [11].

Other interactions of PSMD10


Analytical, diagnostic and therapeutic context of PSMD10


  1. The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53. Higashitsuji, H., Higashitsuji, H., Itoh, K., Sakurai, T., Nagao, T., Sumitomo, Y., Sumitomo, H., Masuda, T., Dawson, S., Shimada, Y., Mayer, R.J., Fujita, J. Cancer Cell (2005) [Pubmed]
  2. Gankyrin: an intriguing name for a novel regulator of p53 and RB. Lozano, G., Zambetti, G.P. Cancer Cell (2005) [Pubmed]
  3. A cleaved form of MAGE-A4 binds to Miz-1 and induces apoptosis in human cells. Sakurai, T., Itoh, K., Higashitsuji, H., Nagao, T., Nonoguchi, K., Chiba, T., Fujita, J. J. Biol. Chem. (2004) [Pubmed]
  4. Novel insights into the INK4-CDK4/6-Rb pathway: counter action of gankyrin against INK4 proteins regulates the CDK4-mediated phosphorylation of Rb. Li, J., Tsai, M.D. Biochemistry (2002) [Pubmed]
  5. Detection of antibodies to human T-lymphotropic virus type 1 (HTLV-1). Fang, C.T., Williams, A.E., Sandler, S.G., Slamon, D.J., Poiesz, B.J. Transfusion (1988) [Pubmed]
  6. Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas. Higashitsuji, H., Itoh, K., Nagao, T., Dawson, S., Nonoguchi, K., Kido, T., Mayer, R.J., Arii, S., Fujita, J. Nat. Med. (2000) [Pubmed]
  7. Gankyrin: a new oncoprotein and regulator of pRb and p53. Dawson, S., Higashitsuji, H., Wilkinson, A.J., Fujita, J., Mayer, R.J. Trends Cell Biol. (2006) [Pubmed]
  8. Radioimmunoassay for protein p28 of murine mammary tumor virus in organs and serum of mice and search for related antigens in human sera and breast cancer extracts. Hendrick, J.C., François, C., Calberg-Bacq, C.M., Colin, C., Franchimont, P., Gosselin, L., Kozma, S., Osterrieth, P.M. Cancer Res. (1978) [Pubmed]
  9. The crystal structure of gankyrin, an oncoprotein found in complexes with cyclin-dependent kinase 4, a 19 S proteasomal ATPase regulator, and the tumor suppressors Rb and p53. Krzywda, S., Brzozowski, A.M., Higashitsuji, H., Fujita, J., Welchman, R., Dawson, S., Mayer, R.J., Wilkinson, A.J. J. Biol. Chem. (2004) [Pubmed]
  10. Gankyrin is an ankyrin-repeat oncoprotein that interacts with CDK4 kinase and the S6 ATPase of the 26 S proteasome. Dawson, S., Apcher, S., Mee, M., Higashitsuji, H., Baker, R., Uhle, S., Dubiel, W., Fujita, J., Mayer, R.J. J. Biol. Chem. (2002) [Pubmed]
  11. The oncoprotein gankyrin negatively regulates both p53 and RB by enhancing proteasomal degradation. Higashitsuji, H., Liu, Y., Mayer, R.J., Fujita, J. Cell Cycle (2005) [Pubmed]
  12. 28,000-dalton polypeptide (p28) of adult T-cell leukemia-associated antigen encoded by 24 S mRNA of human T-cell leukemia virus has an associated protein kinase activity. Kobayashi, N., Koyanagi, Y., Yamamoto, N., Hinuma, Y., Sato, H., Okochi, K., Hatanaka, M. J. Biol. Chem. (1984) [Pubmed]
  13. Overexpression of p28/gankyrin in human hepatocellular carcinoma and its clinical significance. Fu, X.Y., Wang, H.Y., Tan, L., Liu, S.Q., Cao, H.F., Wu, M.C. World J. Gastroenterol. (2002) [Pubmed]
  14. The role of p28GANK in rat oval cells activation and proliferation. Shan, Y.F., Zhou, W.P., Fu, X.Y., Yan, H.X., Yang, W., Liu, S.Q., Cao, H.F., Kang, B., Wu, M.C., Wang, H.Y. Liver Int. (2006) [Pubmed]
  15. Crystallization of gankyrin, an oncoprotein that interacts with CDK4 and the S6b (rpt3) ATPase of the 19S regulator of the 26S proteasome. Krzywda, S., Brzozowski, A.M., Al-Safty, R., Welchman, R., Mee, M., Dawson, S., Fujita, J., Higashitsuji, H., Mayer, R.J., Wilkinson, A.J. Acta Crystallogr. D Biol. Crystallogr. (2003) [Pubmed]
  16. Function of the p86 subunit of eukaryotic initiation factor (iso)4F as a microtubule-associated protein in plant cells. Bokros, C.L., Hugdahl, J.D., Kim, H.H., Hanesworth, V.R., van Heerden, A., Browning, K.S., Morejohn, L.C. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  17. Properties of a surface antigen expressed on activated human thymus-derived lymphocytes. Udey, M.C., Jendrisak, M.D., Parker, C.W. J. Immunol. (1982) [Pubmed]
  18. Membrane protein synthesis in mitogen-stimulated human T lymphocytes. Udey, M.C., Parker, C.W. J. Immunol. (1981) [Pubmed]
  19. Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3. Shen, X., Yang, Y., Liu, W., Sun, M., Jiang, J., Zong, H., Gu, J. FEBS Lett. (2004) [Pubmed]
  20. Negatively regulating mechanism of Sirpalpha1 in hepatocellular carcinoma: an experimental study. Qin, J.M., Yan, H.X., Liu, S.Q., Wan, X.W., Zeng, J.Z., Cao, H.F., Qiu, X.H., Wu, M.C., Wang, H.Y. HBPD INT (2006) [Pubmed]
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