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

Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation. Research Abstract Details 

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Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation. Abstract Text:

Masayuki Kanai,Kazuhiko Hanashiro,Song-Hee Kim,Shuji Hanai,A Hamid Boulares,Masanao Miwa,Kenji Fukasawa,Masayuki Kanai,Kazuhiko Hanashiro,Song-Hee Kim,Shuji Hanai,A Hamid Boulares,Masanao Miwa,Kenji Fukasawa,

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.

Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation. Publishing Authors By Initials

M Kanai,K Hanashiro,SH Kim,S Hanai,AH Boulares,M Miwa,K Fukasawa,M Kanai,K Hanashiro,SH Kim,S Hanai,AH Boulares,M Miwa,K Fukasawa,

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Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Nature cell biology

VOLUME: 9

Page Numbers: 1175-83

Journal Abbreviation: Nat. Cell Biol.

ISSN: 1465-7392

DAY: 23

MONTH: 09

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 100890575

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Grant and Affiliation Information for Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation.

AFFILIATION: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.

Country: England

AGENCY: United States NHLBI

GRANT: HL072889

ACRONYM: HL

MEDLINETA: Nat Cell Biol

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