文章基本信息

标题：p300 regulates p53-dependent apoptosis after DNA damage in colorectal cancer cells by modulation of PUMA/p21 levels
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作者：N. Gopalakrishna Iyer ; Suet-Feung Chin ; Hilal Ozdag 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：19
页码：7386-7391
DOI：10.1073/pnas.0401002101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Activation of the tumor suppressor p53 by DNA damage induces either cell cycle arrest or apoptosis, but what determines the choice between cytostasis and death is not clear. In this report, we show that the E1A-binding p300 nucleoprotein is a key determinant of p53-dependent cell fate in colorectal cancer cells: absence of p300 increases apoptosis in response to DNA damage. In addition, p300-deficient (p300-) cells fail to undergo G1/S arrest after UV irradiation. These abnormalities are associated with prolongation of p53 stability, reduced p53-acetylation, blunting of MDM2 activation, failure to transactivate p21, and a disproportionate increase in PUMA levels. When xenografted, p300- cells are more sensitive to chemotherapy with doxorubicin. These results show that p300 is a key regulator of the p53 response and suggest that p300 inhibition could be used to modulate chemotherapy.