The known molecular players in cell-cycle control are much studied, not only to learn more about this intricate system, but also to understand the molecular features of oncogenic transformation. Infrequently, new players are discovered that change the interpretation of cell-cycle control. Gankyrin is one such player and was discovered in yeast two-hybrid screens as a new proteasomal subunit that interacts specifically with the S6b (rpt3) AAA (ATPase associated with various cellular activities) ATPase, which, with five other AAAs, are present in the so-called base of the 19 S regulator of the 26 S proteasome. Gankyrin is also the first liver oncogene. Gankyrin is found in other complexes that contain Rb (retinoblastoma protein) and the ubiquitin protein ligase Mdm2 (murine double minute 2). Gankyrin increases the hyperphosphorylation of Rb and therefore activates E2F-dependent transcription of DNA synthesis genes. Additionally, gankyrin, by binding to Mdm2, increases the ubiquitylation and degradation of p53 and prevents apoptosis. Gankyrin controls the functions of two major tumour suppressors and, when overexpressed, causes hepatocellular carcinoma.
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Conference Article|
October 25 2006
Gankyrin, the 26 S proteasome, the cell cycle and cancer
R.J. Mayer;
R.J. Mayer
1
*School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, U.K.
1To whom correspondence should be addressed (email John.Mayer@nottingham.ac.uk).
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J. Fujita
J. Fujita
†Department of Clinical Molecular Biology, Graduate School of Medicine, Kyoto University, Shogoin Kawahararacho, Sakyo-Ku, Kyoto 606-8507, Japan
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Publisher: Portland Press Ltd
Received:
May 30 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (5): 746–748.
Article history
Received:
May 30 2006
Citation
R.J. Mayer, J. Fujita; Gankyrin, the 26 S proteasome, the cell cycle and cancer. Biochem Soc Trans 1 October 2006; 34 (5): 746–748. doi: https://doi.org/10.1042/BST0340746
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