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Gankyrin
Gankyrin is a recently discovered oncoprotein that is a component of the 19S regulatory cap of the proteasome. Structurally, it contains a 33-amino acid ankyrin repeat that forms a series of alpha helices.〔Krzywda S, Brzozowski AM, Higashitsuji H, Fujita J, Welchman R, Dawson S, Mayer RJ, Wilkinson AJ. (2004). 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. ''J Biol Chem'' 279(2):1541-5.〕 It plays a key role in regulating the cell cycle via protein-protein interactions with the cyclin-dependent kinase CDK4. It also binds closely to the E3 ubiquitin ligase MDM2, which is a regulator of the degradation of p53 and retinoblastoma protein, both transcription factors involved in tumor suppression and found mutated in many cancers.〔Krzywda S, Brzozowski AM, Al-Safty R, Welchman R, Mee M, Dawson S, Fujita J, Higashitsuji H, Mayer RJ, Wilkinson AJ. (2003). Crystallization of gankyrin, an oncoprotein that interacts with CDK4 and the S6b (rpt3) ATPase of the 19S regulator of the 26S proteasome. ''Acta Crystallogr D Biol Crystallogr'' 59(Pt 7):1294-5.〕 Gankyrin also has an anti-apoptotic effect and is overexpressed in certain types of tumor cells such as hepatocellular carcinoma.〔Higashitsuji H, Liu Y, Mayer RJ, Fujita J. (2005). The oncoprotein gankyrin negatively regulates both p53 and RB by enhancing proteasomal degradation. Cell Cycle 4(10):1335-7.〕
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