Format

Send to

Choose Destination
Cell Rep. 2014 Aug 7;8(3):807-17. doi: 10.1016/j.celrep.2014.06.050. Epub 2014 Jul 24.

The BRCA1-interacting protein Abraxas is required for genomic stability and tumor suppression.

Author information

1
Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
2
Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Genes and Development Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
3
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Genes and Development Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
4
Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
5
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
6
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
7
Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
8
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
9
Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Genes and Development Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA. Electronic address: bwang3@mdanderson.org.

Abstract

Germline mutations of BRCA1 confer hereditary susceptibility to breast and ovarian cancer. However, somatic mutation of BRCA1 is infrequent in sporadic breast cancers. The BRCA1 protein C terminus (BRCT) domains interact with multiple proteins and are required for BRCA1's tumor-suppressor function. In this study, we demonstrated that Abraxas, a BRCA1 BRCT domain-interacting protein, plays a role in tumor suppression. Abraxas exerts its function through binding to BRCA1 to regulate DNA repair and maintain genome stability. Both homozygous and heterozygous Abraxas knockout mice exhibited decreased survival and increased tumor incidence. The gene encoding Abraxas suffers from gene copy loss and somatic mutations in multiple human cancers including breast, ovarian, and endometrial cancers, suggesting that mutation and loss of function of Abraxas may contribute to tumor development in human patients.

PMID:
25066119
PMCID:
PMC4149256
DOI:
10.1016/j.celrep.2014.06.050
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center