Inhibition of Crm1–p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation

被引：0
作者：
Masayuki Kanai
Kazuhiko Hanashiro
Song-Hee Kim
Shuji Hanai
A. Hamid Boulares
Masanao Miwa
Kenji Fukasawa
机构：
[1] H. Lee Moffitt Cancer Center and Research Institute,Department of Cell Biology
[2] University of Cincinnati College of Medicine,Department of Pharmacology
[3] Cincinnati,undefined
[4] Ohio 45267,undefined
[5] USA.,undefined
[6] National Institute of Advanced Industrial Science and Technology,undefined
[7] Louisiana State University Health Sciences Center,undefined
[8] Faculty of Bioscience,undefined
[9] Nagahama Institute of Bio-Science and Technology,undefined
来源：
Nature Cell Biology | 2007年 / 9卷
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摘要：
Poly(ADP-ribose) polymerase 1 (PARP-1) and p53 are two key proteins in the DNA-damage response. Although PARP-1 is known to poly(ADP-ribosyl)ate p53, the role of this modification remains elusive. Here, we identify the major poly(ADP-ribosyl)ated sites of p53 by PARP-1 and find that PARP-1-mediated poly(ADP-ribosyl)ation blocks the interaction between p53 and the nuclear export receptor Crm1, resulting in nuclear accumulation of p53. These findings molecularly link PARP-1 and p53 in the DNA-damage response, providing the mechanism for how p53 accumulates in the nucleus in response to DNA damage. PARP-1 becomes super-activated by binding to damaged DNA, which in turn poly(ADP-ribosyl)ates p53. The nuclear export machinery is unable to target poly(ADP-ribosyl)ated p53, promoting accumulation of p53 in the nucleus where p53 exerts its transactivational function.
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页码：1175 / 1183
页数：8
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