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| A model for p53-induced apoptosis |
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| Author(s): Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B |
| Source: NATURE Volume: 389 Issue: 6648 Pages: 300-305 Published: SEP 18 1997 |
| Times Cited: 1,511 References: 29 |
| Abstract: The inactivation of the p53 gene in a large proportion of human cancers has inspired an intense search for the encoded protein's 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(2). 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. JOHNS HOPKINS ONCOL CTR, BALTIMORE, MD 21231 USA
2. HOWARD HUGHES MED INST, BALTIMORE, MD 21231 USA
3. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV CARDIOL, BALTIMORE, MD 21205 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: XW772 |
| ISSN: 0028-0836 |
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