A model for p53-induced apoptosis

Kornelia Polyak, Yong Xia, Jay L. Zweier, Kenneth W Kinzler, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

The inactivation of the p53 gene in a large proportion of human cancers has inspired an intense search for the encoded proteins physiological and biological properties. Expression of p53 induces either a stable growth arrest or programmed cell death (apoptosis). In human colorectal cancers, the growth arrest is dependent on the transcriptional induction of the protein p21(WAF1/CIP1) (ref: 1), but the mechanisms underlying the development of p53 dependent apoptosis are largely unknown. As the most well documented biochemical property of p53 is its ability to activate transcription of genes, we examined in detail the transcripts induced by p53 expression before the onset of apoptosis. Of 7,202 transcripts identified, only 14 (0.19%) were found to be markedly increased in p53-expressing cells compared with control cells. Strikingly, many of these genes were predicted to encode proteins that could generate or respond to oxidative stress, including one that is implicated in apoptosis in plant meristems. These observations stimulated additional biochemical and pharmacological experiments suggesting that p53 results in apoptosis through a three-step process: (1) the transcriptional induction of redox-related genes; (2) the formation of reactive oxygen species; and (3) the oxidative degradation of mitochondrial components, culminating in cell death.

Original languageEnglish (US)
Pages (from-to)300-305
Number of pages6
JournalNature
Volume389
Issue number6648
DOIs
StatePublished - 1997

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Apoptosis
Cell Death
Genes
Proteins
Meristem
p53 Genes
Growth
Oxidation-Reduction
Colorectal Neoplasms
Reactive Oxygen Species
Oxidative Stress
Pharmacology
Neoplasms

ASJC Scopus subject areas

  • General

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A model for p53-induced apoptosis. / Polyak, Kornelia; Xia, Yong; Zweier, Jay L.; Kinzler, Kenneth W; Vogelstein, Bert.

In: Nature, Vol. 389, No. 6648, 1997, p. 300-305.

Research output: Contribution to journalArticle

Polyak, K, Xia, Y, Zweier, JL, Kinzler, KW & Vogelstein, B 1997, 'A model for p53-induced apoptosis', Nature, vol. 389, no. 6648, pp. 300-305. https://doi.org/10.1038/38525
Polyak, Kornelia ; Xia, Yong ; Zweier, Jay L. ; Kinzler, Kenneth W ; Vogelstein, Bert. / A model for p53-induced apoptosis. In: Nature. 1997 ; Vol. 389, No. 6648. pp. 300-305.
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