Zbtb4 Represses Transcription of P21CIP1 and Controls the Cellular Response to P53 Activation

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2008 May 3

PMID 18451802

Citations 55

Authors

Axel Weber

Judith Marquardt

David Elzi

Nicole Forster

Sven Starke

Andre Glaum

Daisuke Yamada

Pierre-Antoine Defossez

Jeffrey Delrow

Robert N Eisenman

Holger Christiansen

Martin Eilers

Affiliations

Soon will be listed here.

Abstract

In response to stimuli that activate p53, cells can undergo either apoptosis or cell cycle arrest, depending on the precise pattern of p53 target genes that is activated. We show here that Zbtb4, a transcriptional repressor protein, associates with the Sin3/histone deacetylase co-repressor and represses expression of P21CIP1 as part of a heterodimeric complex with Miz1. In vivo, expression of ZBTB4 is downregulated in advanced stages of multiple human tumours. In cell culture, depletion of ZBTB4 promotes cell cycle arrest in response to activation of p53 and suppresses apoptosis through regulation of P21CIP1, thereby promoting long-term cell survival. Our data suggest that Zbtb4 is a critical determinant of the cellular response to p53 activation and reinforce the notion that p21Cip1 can provide an essential survival signal in cells with activated p53.

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