CARF (collaborator of ARF) interacts with HDM2: Evidence for a novel regulatory feedback regulation of CARF-p53-HDM2-p21WAF1 pathway
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- Published online on: March 1, 2008 https://doi.org/10.3892/ijo.32.3.663
- Pages: 663-671
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Abstract
We initially cloned CARF (collaborator of ARF), as a novel ARF-binding protein by a yeast interaction screen. It also interacts with p53 directly leading to ARF-independent enhancement of p53 function and in turn undergoes a negative feedback regulation. Herein we report that i) CARF interacts with HDM2 and undergoes degradation by an HDM2-dependent proteasome pathway, and ii) it acts as a transcriptional repressor of HDM2. By overexpression and silencing studies, we demonstrated that CARF exerts a vital control on the p53-HDM2-p21WAF1 pathway that is frequently altered in cancer cells.