Related Experiment Video
Updated: Jul 6, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing MDM2
Wensheng Yang1, David T Dicker, Jiandong Chen
1Laboratory of Molecular Oncology and Cell Cycle Regulation, Department of Medicine (Hematology/Oncology), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
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.
Related Concept Videos
Abnormal Proliferation
DNA Damage can Stall the Cell Cycle
DNA Damage Can Stall the Cell Cycle
Negative Regulator Molecules
Inhibition of Cdk Activity
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...

