Work

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

Year: 2008

Type: article

Abstract: CARP1 and CARP2 proteins (CARPs) 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 CARPs associate with MDM2. We provide evidence that CARPs stabilize MDM2 by inhibiting MDM2 self-ubiquitination. CARPs together with MDM2 enhance p53 degradation, thereby inhibiting p53-mediated cell death. CARP protein levels correlate with MDM2 levels including under hypoxia where both are reduced. CARP2 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 CARPs, although overexpression of CARP2 enhances MDM2/MDMX interaction. Taken together, our study identifies novel mechanisms by which CARP proteins regulate the p53 signaling pathway.

Source: Cell Cycle

DOI: 10.4161/cc.7.5.5701

Authors: Wensheng Yang, David T. Dicker, Jiandong Chen, Wafik S. El-Deiry

Institutions: University of Pennsylvania, Abramson Cancer Center, Moffitt Cancer Center

Language: English

Topic: Cancer-related Molecular Pathways

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Rutgers Cancer Institute of New Jersey, National Institutes of Health, National Cancer Institute