The research focuses on BRCA1-dependent signaling pathways, whose dysfunction leads to the familial and sporadic breast and ovarian cancer. In particular, this proposal outlines studies on the function of BRCA1 proteins in a transcription factor complex containing p53, which plays a crucial role in cell cycle checkpoint. We have obtained two novel findings: binding of BRCA1 to p53, and stimulation of p53- dependent gene expression by BRCA1. The combined action of BRCA1 and p53 efficiently enhanced p53-dependent gene expression, strongly suggesting a significant role of BRCA1 in cell cycle checkpoint. We propose: i) to further define the function of the BRCA1/p53 complex, and ii) to investigate the mechanisms underlying p53-dependent gene expression.
Specific Aims are i) to investigate the regulation of BRCA-mediated gene expression, 2) to characterize the minimal binding region of BRCA1 and p53, and 3) to investigate the role of BRCA1 phosphorylation to stimulate p53-dependent gene expression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA079892-01
Application #
2736706
Study Section
Pathology B Study Section (PTHB)
Program Officer
Gallahan, Daniel L
Project Start
1998-12-11
Project End
2002-11-30
Budget Start
1998-12-11
Budget End
1999-11-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
Fernández-Jaén, Alberto; Álvarez, Sara; So, Eui Young et al. (2016) Mutations in BRAT1 cause autosomal recessive progressive encephalopathy: Report of a Spanish patient. Eur J Paediatr Neurol 20:421-5
Sancho, Sara Cuesta; Ouchi, Toru (2015) Cell Differentiation and Checkpoint. Int J Cancer Res Mol Mech 1:
So, Eui Young; Ouchi, Mutsuko; Cuesta-Sancho, Sara et al. (2015) Tumor suppression by resistant maltodextrin, Fibersol-2. Cancer Biol Ther 16:460-5
So, Eui Young; Ouchi, Toru (2014) Decreased DNA repair activity in bone marrow due to low expression of DNA damage repair proteins. Cancer Biol Ther 15:906-10
Shionome, Yoshimi; Yan, Li; Liu, Song et al. (2013) Integrity of p53 associated pathways determines induction of apoptosis of tumor cells resistant to Aurora-A kinase inhibitors. PLoS One 8:e55457
Shionome, Yoshimi; Lin, Wen-Hsing; Shiao, Hui-Yi et al. (2013) A novel aurora-A inhibitor, BPR1K0609S1, sensitizes colorectal tumor cells to 5-fluorofracil (5-FU) treatment. Int J Biol Sci 9:403-11
Kang, M A; So, E-Y; Simons, A L et al. (2012) DNA damage induces reactive oxygen species generation through the H2AX-Nox1/Rac1 pathway. Cell Death Dis 3:e249
Kang, Meyke Ausman; So, Eui-Young; Ouchi, Toru (2012) Deregulation of DNA damage response pathway by intercellular contact. J Biol Chem 287:16246-55
Jeon, Gye Sun; Kim, Ki Yoon; Hwang, Yu Jin et al. (2012) Deregulation of BRCA1 leads to impaired spatiotemporal dynamics of ?-H2AX and DNA damage responses in Huntington's disease. Mol Neurobiol 45:550-63
So, E Y; Ausman, M; Saeki, T et al. (2011) Phosphorylation of SMC1 by ATR is required for desferrioxamine (DFO)-induced apoptosis. Cell Death Dis 2:e128

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