BRCA1 tumor suppression depends on BRCT phosphoprotein binding, but not its E3 ligase activity

Shakya, R., Reid, L. J., Reczek, C. R., Cole, F., Egli, D., Lin, C. S., DeRooij, D. G., Hirsch, S., Ravi, K., Hicks, J. B., Szabolcs, M., Jasin, M., Baer, R., Ludwig, T. (October 2011) BRCA1 tumor suppression depends on BRCT phosphoprotein binding, but not its E3 ligase activity. Science, 334 (6055). pp. 525-528. ISSN 00368075 (ISSN)

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Abstract

Germline mutations of the breast cancer 1 (BRCA1) gene are a major cause of familial breast and ovarian cancer. The BRCA1 protein displays E3 ubiquitin ligase activity, and this enzymatic function is thought to be required for tumor suppression. To test this hypothesis, we generated mice that express an enzymatically defective Brca1. We found that this mutant Brca1 prevents tumor formation to the same degree as does wild-type Brca1 in three different genetically engineered mouse (GEM) models of cancer. In contrast, a mutation that ablates phosphoprotein recognition by the BRCA C terminus (BRCT) domains of BRCA1 elicits tumors in each of the three GEM models. Thus, BRCT phosphoprotein recognition, but not the E3 ligase activity, is required for BRCA1 tumor suppression.

Item Type:	Paper
Subjects:	diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > suppressor bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > ubiquitin ligase
CSHL Authors:	Hicks, James B.
Communities:	CSHL Cancer Center Program > Cancer Genetics CSHL Cancer Center Shared Resources > DNA Sequencing Service CSHL Cancer Center Shared Resources > Instrumentation Service CSHL labs > Hicks lab
Depositing User:	Matt Covey
Date:	28 October 2011
Date Deposited:	06 Feb 2013 14:41
Last Modified:	20 Jul 2021 20:40
PMCID:	PMC3904783
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/27192

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