CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing MDM2.

and proteins are E3 ligases that target p53 as well as phospho-p53 for degradation. Because MDM2 is a critical regulator of p53 turnover, we investigated and found that associate with MDM2. We provide evidence that Cduanyu37s stabilize MDM2 by inhibiting MDM2 self-ubiquitination. Cduanyu37s together with MDM2 enhance p53 degradation, thereby inhibiting p53-mediated cell death. protein levels correlate with MDM2 levels including under hypoxia where both are reduced. Cduanyu372 was found to target 14-3-3sigma for degradation, leading to MDM2 stabilization. MDMX, a homolog of MDM2, is not absolutely required for MDM2 stabilization by although overexpression of Cduanyu372 enhances MDM2/MDMX interaction. Taken together, our study identifies novel mechanisms by which Cduanyu37 proteins regulate the p53 signaling pathway.

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