Gankyrin: A potential target for drug therapy against hepatocellular carcinoma

Shashank Gandhi, Veena Puri, Sanjeev Puri

Center for System Biology and Bioinformatics, U.I.E.A.S.T, Panjab University, Chandigarh, India.
Department of Biotechnology, University Institute of Engineering and Technology, Panjab University, Chandigarh, India.

DOI: 10.4236/jbise.2012.58059                

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.

Keywords

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

Conflicts of Interest

The authors declare no conflicts of interest.

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