14-3-3σ is a p53-regulated inhibitor of G2/M progression

Heiko Hermeking, Christoph Lengauer, Kornelia Polyak, Tong Chuan He, Lin Zhang, Sam Thiagalingam, Kenneth W Kinzler, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

Exposure of colorectal cancer (CRC) cells to ionizing radiation results in a cell-cycle arrest in G1 and G2. The G1 arrest is due to p53-mediated induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/SDI1, but the basis for the G2 arrest is unknown. Through a quantitative analysis of gene expression patterns in CRC cell lines, we have discovered that 14-3-3σ is strongly induced by 7 irradiation and other DNA-damaging agents. The induction of 14-3-3σ is mediated by a p53-responsive element located 1.8 kb upstream of its transcription start site. Exogenous introduction of 14-3-3σ into cycling cells results in a G2 arrest. As the fission yeast 14-3-3 homologs rad24 and rad25 mediate similar checkpoint effects, these results document a molecular mechanism for G2/M control that is conserved throughout eukaryotic evolution and regulated in human cells by p53.

Original languageEnglish (US)
Pages (from-to)3-11
Number of pages9
JournalMolecular Cell
Volume1
Issue number1
StatePublished - Dec 1997

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Colorectal Neoplasms
G2 Phase Cell Cycle Checkpoints
G1 Phase Cell Cycle Checkpoints
Cyclin-Dependent Kinases
Schizosaccharomyces
Transcription Initiation Site
Gene Expression Profiling
Ionizing Radiation
Cell Line
DNA

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Hermeking, H., Lengauer, C., Polyak, K., He, T. C., Zhang, L., Thiagalingam, S., ... Vogelstein, B. (1997). 14-3-3σ is a p53-regulated inhibitor of G2/M progression. Molecular Cell, 1(1), 3-11.

14-3-3σ is a p53-regulated inhibitor of G2/M progression. / Hermeking, Heiko; Lengauer, Christoph; Polyak, Kornelia; He, Tong Chuan; Zhang, Lin; Thiagalingam, Sam; Kinzler, Kenneth W; Vogelstein, Bert.

In: Molecular Cell, Vol. 1, No. 1, 12.1997, p. 3-11.

Research output: Contribution to journalArticle

Hermeking, H, Lengauer, C, Polyak, K, He, TC, Zhang, L, Thiagalingam, S, Kinzler, KW & Vogelstein, B 1997, '14-3-3σ is a p53-regulated inhibitor of G2/M progression', Molecular Cell, vol. 1, no. 1, pp. 3-11.
Hermeking H, Lengauer C, Polyak K, He TC, Zhang L, Thiagalingam S et al. 14-3-3σ is a p53-regulated inhibitor of G2/M progression. Molecular Cell. 1997 Dec;1(1):3-11.
Hermeking, Heiko ; Lengauer, Christoph ; Polyak, Kornelia ; He, Tong Chuan ; Zhang, Lin ; Thiagalingam, Sam ; Kinzler, Kenneth W ; Vogelstein, Bert. / 14-3-3σ is a p53-regulated inhibitor of G2/M progression. In: Molecular Cell. 1997 ; Vol. 1, No. 1. pp. 3-11.
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