Novel BRCA2-interacting protein BJ-HCC-20A inhibits the induction of apoptosis in response to DNA damage.
The major hereditary breast cancer susceptibility gene BRCA2 is associated with familial breast and ovarian cancer. BRCA2 plays a role in DNA repair, transcription, cell cycle regulation, maintenance of genomic stability in response to DNA damage, centrosome regulation, and cytokinesis. To further understand the function of BRCA2, we used a ... yeast two-hybrid method and identified a novel BRCA2-interacting protein, BJ-HCC-20A, which is reported to be a potential cancer-testis antigen. We confirmed the interaction between endogenous BJ-HCC-20A and BRCA2 in mammalian cells, and showed that BJ-HCC-20A interacts with a portion of the highly conserved region of BRCA2 in various mammals, and M phase-specific phosphorylation of the binding region of BRCA2 modulates BJ-HCC-20A binding. Overexpression of BJ-HCC-20A increases cell growth, and downregulation of endogenous BJ-HCC-20A expression using small interfering RNA suppresses cell growth and leads to the induction of apoptosis. Importantly, the BJ-HCC-20A mRNA level is downregulated by adriamycin (ADR)-induced DNA damage and depletion of BJ-HCC-20A expression by small interfering RNA promotes the reduction of BRCA2 expression and enhances cell apoptosis in response to DNA damage. Additionally, the recovery of BJ-HCC-20A expression in ADR-induced DNA damage inhibits ADR-induced apoptosis. The data suggest that BJ-HCC-20A promotes cell growth and may regulate the induction of cell apoptosis in response to DNA damage in cooperation with BRCA2 in an M phase-dependent manner. Therefore, we speculate that targeting BJ-HCC-20A may aid in the treatment of breast tumors.
Mesh Terms:
Amino Acid Sequence, Animals, Antibiotics, Antineoplastic, Apoptosis, Apoptosis Regulatory Proteins, BRCA2 Protein, Cell Cycle Proteins, Cell Line, Tumor, Cell Proliferation, Conserved Sequence, DNA Damage, Down-Regulation, Doxorubicin, Humans, Mice, Phosphorylation, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, RNA, Messenger, RNA, Small Interfering, Two-Hybrid System Techniques
Amino Acid Sequence, Animals, Antibiotics, Antineoplastic, Apoptosis, Apoptosis Regulatory Proteins, BRCA2 Protein, Cell Cycle Proteins, Cell Line, Tumor, Cell Proliferation, Conserved Sequence, DNA Damage, Down-Regulation, Doxorubicin, Humans, Mice, Phosphorylation, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, RNA, Messenger, RNA, Small Interfering, Two-Hybrid System Techniques
Cancer Sci.
Date: Apr. 01, 2008
PubMed ID: 18307534
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