Potentiality of phosphorylation of BRCA1 at Ser 1524 to activate p21 in response to X-ray irradiation

Potentiality of phosphorylation of BRCA1 at Ser 1524 to activate p21 in response to X-ray irradiation 1 2 3 first-author 1 2 corresp Corresponding author. E-mail: zhangh@impcas.ac.cn Corresponding author. E-mail: zhangh@impcas.ac.cn zhangh@impcas.ac.cn 1 2 3 4 1 2 1 2 3 Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000, China Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000, China Graduate School of Chinese Academy of Sciences, Beijing 100049, China Graduate School of Chinese Academy of Sciences, Beijing 100049, China Department of Radiotherapy, Gansu Tumor Hospital, Lanzhou 730050, China Department of Radiotherapy, Gansu Tumor Hospital, Lanzhou 730050, China The breast and ovarian cancer susceptibility gene BRCA1 encodes a nuclear phosphoprotein, which functions as a tumor suppressor gene. Many studies suggested that multiple functions of BRCA1 may contribute to its tumor suppressor activity, including roles in cell cycle checkpoints, apoptosis and transcription. It is postulated that phosphorylation of BRCA1 is an important means by which its cellular functions are regulated. In this study, we employed phospho-Ser-specific antibody recognizing Ser-1524 to study BRCA1 phosphorylation under conditions of DNA damage and the effects of phosphorylation on BRCA1 functions. The results showed that 10 Gy X-ray treatment significantly induced phosphorylation of Ser-1524 but not total BRCA1 protein levels. The expression both of p53 and p21 increased after irradiation, but ionizing radiation (IR) -induced activation of p21 was prior to that of p53. The percentages of G0/G1 phase remarkably increased after IR. In addition, no detectable levels of 89 kDa fragment of PARP, a marker of apoptotic cells, were observed. Data implied that IR-induced phosphorylation of BRCA1 at Ser-1524 might activate p21 protein, by which BRCA1 regulated cell cycle , but play no role in apoptosis. BRCA1 Phosphorylation Cell cycle Apoptosis References Couch F J , DeShano M L , Blackwood M A , et al . N Engl J Med , 1997 , 336 : 1409 - 1415 N Engl J Med Kerr P , Ashworth A . Curr Biol , 2001 , 11 : R668 - 676 Curr Biol Venkitaraman A R . Cell , 2002 , 108 : 171 - 182 Cell Venkitaraman A R . J Cell Sci , 2001 , 114 ( Pt ): 3591 - 3598 J Cell Sci Zhang J , Powell S N . Mol Cancer Res , 2005 , 3 : 531 - 539 Mol Cancer Res Zhang H , Somasundaram K , Peng Y , et al . Oncogene , 1998 , 16 : 1713 - 1721 Oncogene Chai YL , Cui J , Shao N , et al . Oncogene , 1999 , 18 : 263 - 268 Oncogene MacLachlan T K , Takimoto R , El-Deiry W S . Mol Cell Biol , 2002 , 22 : 4280 - 4292 . Mol Cell Biol Lee J S , Collins K M , Brown A L , et al . Nature , 2000 , 404 : 201 - 204 . Nature Gatei M , Scott S P , Filippovitch I , et al . Cancer Res , 2000 , 60 : 3299 - 3304 . Cancer Res Gatei M , Zhou B B , Hobson K , et al . J Biol Chem , 2001 , 276 : 17276 - 17280 . J Biol Chem Fabbro M , Savage K , Hobson K , et al . J Biol Chem , 2004 , 279 : 31251 - 31258 . J Biol Chem Somasundaram K , Zhang H , Zeng Y X , et al . Nature , 1997 , 389 : 187 - 190 . Nature Wang Y , Cortez D , Yazdi P , et al . Genes Dev , 2000 , 14 : 927 - 939 . Genes Dev Lou Z , Chini C C , Minter-Dykhouse K , et al . J Biol Chem , 2003 , 278 : 13599 - 13602 . J Biol Chem Zhou B B , Elledge S J . Nature , 2000 , 408 : 433 - 439 . Nature Zhang J , Willers H , Feng Z , et al . Mol Cell Biol , 2004 , 24 : 708 - 718 . Mol Cell Biol MacLachlan T K , Somasundaram K , Sgagias M , et al . J Biol Chem , 2000 , 275 : 2777 - 2785 . J Biol Chem Gatei M , Zhou BB , Hobson K , et al . J Biol Chem , 2001 , 276 : 17276 - 17280 . J Biol Chem Chen Y , Farmer AA , Chen CF , et al . Cancer Res , 1996 , 56 : 3168 - 3172 . Cancer Res Ruffner H , Verma M . Proc Natl Acad Sci USA ., 1997 , 94 : 7138 - 7143 . Proc Natl Acad Sci USA 10.1016/S1001-8042(08)60040-8 Q6 Supported by grants from the National Natural Science Foundation of China (10675151) , the Key Scientific Technology Research Projects of Gansu Province (O702NKDA045) , the Scientific Technology Research Project of Lanzhou-Chinese Academy of Sciences (07-2-07) and Western Talent Program of Chinese Academy of Sciences (0760160XBO, 0860260XBO) . 2008-03-05 2008-06-20 2021-01-19 2008 Nuclear Science and Techniques 03 19