Involvement of p85 in p53-dependent apoptotic response to oxidative stress

Yin, Yuxin and Terauchi, Yasuo and Solomon, Gregory G and Aizawa, Shinichi and Rangarajan, PN and Yazaki, Yoshio and Kadowaki, Takashi and Carl Barrett, J (1998) Involvement of p85 in p53-dependent apoptotic response to oxidative stress. In: Nature, 391 (6668). pp. 707-710.

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Abstract

Reactive oxygen species have damaging effects on cellular components and so trigger defensive responses by the cell and even programmed cell death, although the mechanisms by which mammalian cells transmit signals in response to oxidative damage are unknown. We report here that the protein p85, a regulator of the signalling protein phosphatidyl-3-OH kinase (PI(3)K), participates in the cell death process that is induced in response to oxidative stress and that this role of p85 in apoptosis does not involve PI(3)K. We show that disruption of p85 by homologous recombination impairs the cellular apoptotic response to oxidative stress. Because the protein p53 is required for cell death induced by oxidative damage, we examined the relation between p85 and p53. Using a chimaeric p53 fusion protein with the oestrogen receptor (p53ER) to supply p53 (p53 is induced upon binding of p53ER to oestradiol) in a p53-deficient cell line, we found that p85 is upregulated by p53 and that its involvement in p53-mediated apoptosis is independent of PI(3)K. We propose that p85 acts as a signal transducer in the cellular response to oxidative stress, mediating cell death regulated by p53.

Item Type:	Journal Article
Publication:	Nature
Publisher:	Nature Publishing Group
Additional Information:	Copyright of this article belongs to Nature Publishing Group.
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	27 Aug 2009 04:20
Last Modified:	19 Sep 2010 05:25
URI:	http://eprints.iisc.ac.in/id/eprint/18790

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