Gankyrin: an intriguing name for a novel regulator of p53 and RB.
The RB and p53 tumor suppressors lie at the heart of cancer biology, and inactivation of both pathways is seemingly essential for tumor development. 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. 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. These important findings implicate gankyrin as a dual-purpose negative regulator of RB and p53, thereby identifying gankyrin as a rational cancer therapeutic target.
Lozano
Guillermina
G
The University of Texas M.D. Anderson Cancer Center, Department of Molecular Genetics, Section of Cancer Genetics, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Zambetti
Gerard P
GP
D017487:Ankyrins / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D016335:Zinc Fingers
D017487:Ankyrins; D009687:Nuclear Proteins; C403591:PSMD10 protein, human; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D046988:Proteasome Endopeptidase Complex