Abstract：
:Gankyrin is an ankyrin repeat oncoprotein commonly overexpressed in hepatocellular carcinomas. Gankyrin interacts with the S6 proteasomal ATPase and accelerates the degradation of the tumor suppressor Rb. We show here that gankyrin has an antiapoptotic activity in cells exposed to DNA damaging agents. Downregulation of gankyrin induces apoptosis in cells with wild-type p53. In vitro and in vivo experiments revealed that gankyrin binds to Mdm2, facilitating p53-Mdm2 binding, and increases ubiquitylation and degradation of p53. Gankyrin also enhances Mdm2 autoubiquitylation in the absence of p53. Downregulation of gankyrin reduced amounts of Mdm2 and p53 associated with the 26S proteasome. Thus, gankyrin is a cofactor that increases the activities of Mdm2 on p53 and probably targets polyubiquitylated p53 into the 26S proteasome.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Higashitsuji H,Higashitsuji H,Itoh K,Sakurai T,Nagao T,Sumitomo Y,Masuda T,Dawson S,Shimada Y,Mayer RJ,Fujita Jdoi
10.1016/j.ccr.2005.06.006keywords:
subject
Has Abstractpub_date
2005-07-01 00:00:00pages
75-87issue
1eissn
1535-6108issn
1878-3686pii
S1535-6108(05)00194-7journal_volume
8pub_type
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