Negative Regulation of Tumor Suppressor P53 by MicroRNA MiR-504

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2010 Jun 15

PMID 20542001

Citations 165

Authors

Wenwei Hu

Chang S Chan

Rui Wu

Cen Zhang

Yvonne Sun

Jun S Song

Laura H Tang

Arnold J Levine

Zhaohui Feng

Affiliations

Soon will be listed here.

Abstract

Tumor suppressor p53 plays a central role in tumor prevention. p53 protein levels and activity are under a tight and complex regulation in cells to maintain the proper function of p53. MicroRNAs play a key role in the regulation of gene expression. Here we report the regulation of p53 through miR-504. miR-504 acts as a negative regulator of human p53 through its direct binding to two sites in the p53 3' untranslated region. Overexpression of miR-504 decreases p53 protein levels and functions in cells, including p53 transcriptional activity, p53-mediated apoptosis, and cell-cycle arrest in response to stress, and furthermore promotes tumorigenecity of cells in vivo. These results demonstrate the direct negative regulation of p53 by miR-504 as a mechanism for p53 regulation in cells, which highlights the importance of microRNAs in tumorigenesis.

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