Letter abstract
Nature Cell Biology 9, 1175 - 1183 (2007)
Published online: 23 September 2007 | doi:10.1038/ncb1638
Inhibition of Crm1–p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation
Masayuki Kanai1,2, Kazuhiko Hanashiro1,2, Song-Hee Kim2, Shuji Hanai3, A. Hamid Boulares4, Masanao Miwa5 & Kenji Fukasawa1,2
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.
- H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
- Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
- National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan.
- Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
- Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan.
Correspondence to: Kenji Fukasawa1,2 e-mail: kenji.fukasawa@uc.edu
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