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Repression of BRCA1 through a Feedback Loop Involving p53

MacLachlan, Timothy K. ; Dash, Bipin C. ; Dicker, David T. ; El-Deiry, Wafik S.

The Journal of biological chemistry, 2000-10, Vol.275 (41), p.31869-31875 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Repression of BRCA1 through a Feedback Loop Involving p53
Autor: MacLachlan, Timothy K. ; Dash, Bipin C. ; Dicker, David T. ; El-Deiry, Wafik S.
Assuntos: adriamycin ; Ataxia Telangiectasia Mutated Proteins ; BRCA1 gene ; BRCA1 Protein - genetics ; BRCA1 Protein - metabolism ; Cell Cycle Proteins ; DNA Damage - drug effects ; DNA-Binding Proteins ; Down-Regulation - drug effects ; Doxorubicin - pharmacology ; Feedback ; Flow Cytometry ; Gene Expression Regulation, Neoplastic - drug effects ; Genes, BRCA1 - genetics ; Genes, Reporter ; Humans ; mitomycin ; Mitomycin - pharmacology ; mitomycin C ; Oncogene Proteins, Viral - genetics ; Oncogene Proteins, Viral - metabolism ; Promoter Regions, Genetic - genetics ; Protein-Serine-Threonine Kinases - genetics ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Transfection ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumor Suppressor Proteins
É parte de: The Journal of biological chemistry, 2000-10, Vol.275 (41), p.31869-31875
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Descrição: The BRCA1 and p53 tumor suppressors have been shown to interact and cooperate to activate transcription of p53-responsive genes. In this study, we show that BRCA1 is initially up-regulated, followed by a reduction to below basal levels in response to treatment with the DNA-damaging agents adriamycin and mitomycin C, and that the reduction of BRCA1 expression is dependent on the presence of wild-type p53. Elimination of p53 by expression of human papilloma virus E6 resulted in an inability to down-regulate BRCA1 in response to adriamycin. Ectopic expression of p53 resulted in a rapid decrease in BRCA1 protein and RNA levels and BRCA1promoter-driven luciferase activity even in null p21 cells deficient in p53-dependent G1 arrest. ATM−/− lymphoblastoid cells were deficient in their ability to reduce BRCA1 protein in response to DNA damage, whereas the wild-type counterparts reduced BRCA1 protein levels after exposure to adriamycin. These results, in conjunction with others, suggest a loop wherein BRCA1 initially participates in accumulation of p53 protein, whereas later p53 acts to reduce BRCA1 expression.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Repression of BRCA1 through a Feedback Loop Involving p53

MacLachlan, Timothy K. ; Dash, Bipin C. ; Dicker, David T. ; El-Deiry, Wafik S.

United States: Elsevier Inc

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