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  • The EMBO Journal (2008) 27, 1563 - 1574
  • doi:10.1038/emboj.2008.85

Published online: 1 May 2008

Zbtb4 represses transcription of P21CIP1 and controls the cellular response to p53 activation

Axel Weber1,2,a, Judith Marquardt1,a, David Elzi3,a, Nicole Forster1,a, Sven Starke2, Andre Glaum2, Daisuke Yamada4, Pierre-Antoine Defossez4, Jeffrey Delrow3, Robert N Eisenman3, Holger Christiansen2 and Martin Eilers1

  1. Institute of Molecular Biology and Tumour Research (IMT), Marburg, Germany
  2. Center for Children's Medicine, University Hospital Marburg and Giessen, Marburg, Germany
  3. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  4. CNRS UMR218, Institut Curie, Paris, France

Correspondence to:

Martin Eilers, Institute of Molecular Biology and Tumour Research, Phillips University Marburg, Universität Marburg, Emil-Mannkopff-Str. 2, Marburg 35033, Germany. Tel.: +49 6421 286 6410; Fax: +49 6421 286 5196; E-mail: eilers@imt.uni-marburg.de

aThese authors contributed equally to this work

Received 19 February 2008; Accepted 2 April 2008

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.

  • Keywords:

    • apoptosis,
    • cell cycle arrest,
    • Miz1,
    • p21Cip1,
    • p53