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Higashitsuji H., Higashitsuji H., Itoh K., Sakurai T., Nagao, T., Sumitomo H., Masuda T., Dawson S., Shimada Y., Mayer R.J., and Fujita J. (2005) The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53. Cancer Cell, 8, 75-87. doi:10.1016/j.ccr.2005.06.006

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• TITLE: Gankyrin: A potential target for drug therapy against hepatocellular carcinoma

  AUTHORS: Shashank Gandhi, Veena Puri, Sanjeev Puri

  KEYWORDS: Hepatocellular Carcinoma; Murine Double Minute-2; p53; Tumor Suppressor Protein; Gankyrin

  JOURNAL NAME: Journal of Biomedical Science and Engineering, Vol.5 No.8, July 31, 2012

  ABSTRACT: Hepatocellular Carcinoma is a primary malignant tumor of the liver and gankyrin is an oncoprotein over-expressed in hepatocellular carcinoma. It has been found that Gankyrin protein reduces the level of p53 protein by increasing its ubiquitylation and degradation, following a MDM-2 mediated pathway. Interaction of gankyrin with MDM2 enhances the ubiquitylation of p53. Independent study of this protein molecule revealed that it is identical to the p28 subunit of the 26S proteasome, having seven similar alpha helical ankyrin repeats. Gankyrin also binds to the Tumor Suppressor Protein (TSP) Retinoblastoma (RB), thereby accelerating its phosphorylation and proteasomal degradation. Blocking the expression of Gankyrin with MDM2 in cases of Hepatocellular Carcinoma (HCC) promoted apoptosis in cancer cells. Hence, Gankyrin can be used as a potential target for drug therapy against Hepatocellular Carcinoma.