XPC Promotes MDM2-mediated Degradation of the P53 Tumor Suppressor

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2013 Nov 22

PMID 24258024

Citations 12

Authors

Jing Yan Krzeszinski

Vitnary Choe

Jia Shao

Xin Bao

Haili Cheng

Shiwen Luo

Keke Huo

Hai Rao

Affiliations

Soon will be listed here.

Abstract

Although ubiquitin receptor Rad23 has been implicated in bringing ubiquitylated p53 to the proteasome, how Rad23 recognizes p53 remains unclear. We demonstrate that XPC, a Rad23-binding protein, regulates p53 turnover. p53 protein in XPC-deficient cells remains ubiquitylated, but its association with the proteasome is drastically reduced, indicating that XPC regulates a postubiquitylation event. Furthermore, we found that XPC participates in the MDM2-mediated p53 degradation pathway via direct interaction with MDM2. XPC W690S pathogenic mutant is specifically defective for MDM2 binding and p53 degradation. p53 is known to become stabilized following UV irradiation but can be rendered unstable by XPC overexpression, underscoring a critical role of XPC in p53 regulation. Elucidation of the proteolytic role of XPC in cancer cells will help to unravel the detailed mechanisms underlying the coordination of DNA repair and proteolysis.

Citing Articles

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