Foxp3 Expression in P53-dependent DNA Damage Responses

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Jan 16

PMID 20075077

Citations 26

Authors

Da-Jung Jung

Dong-Hoon Jin

Seung-Woo Hong

Jee-Eun Kim

Jae-Sik Shin

Daejin Kim

Byung-Joo Cho

Young-Il Hwang

Jae-Seung Kang

Wang-Jae Lee

Affiliations

Soon will be listed here.

Abstract

The forkhead transcription factor, Foxp3, is thought to act as a master regulator that controls (suppresses) expression of the breast cancer oncogenes, SKP2 and HER-2/ErbB2. However, the mechanisms that regulate Foxp3 expression and thereby modulate tumor development remain largely unexplored. Here, we demonstrate that Foxp3 up-regulation requires p53 function, showing that Foxp3 expression is directly regulated by p53 upon DNA damage responses in human breast and colon carcinoma cells. Treatment with the genotoxic agents, doxorubicin or etoposide, induced Foxp3 expression in p53-positive carcinoma cells, but not in cells lacking p53 function. Furthermore, knock down of endogenous wild-type p53 using RNA interference abrogated Foxp3 induction by genotoxic agents, and exogenous expression of p53 in cells lacking p53 restored the responsiveness of Foxp3 to DNA-damaging stresses. In addition, Foxp3 knock down blunted the p53-mediated growth inhibitory response to DNA-damaging agents. These results suggest that induction of Foxp3 in the context of tumor suppression is regulated in a p53-dependent manner and implicate Foxp3 as a key determinant of cell fate in p53-dependent DNA damage responses.

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