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

Reena Shakya, Latarsha J. Reid, Colleen R. Reczek, Francesca Cole, Dieter Egli, Chyuan Sheng Lin, Dirk G. DeRooij, Steffen Hirsch, Kandasamy Ravi, James B. Hicks, Matthias Szabolcs, Maria Jasin, Richard Baer*, Thomas Ludwig

*Corresponding author for this work

Research output: Contribution to journalArticle

157 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)525-528
Number of pages4
JournalScience
Volume334
Issue number6055
DOIs
StatePublished - Oct 28 2011

ASJC Scopus subject areas

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    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. (2011). BRCA1 tumor suppression depends on BRCT phosphoprotein binding, but not its E3 ligase activity. Science, 334(6055), 525-528. https://doi.org/10.1126/science.1209909