Endogenous Purification Reveals GREB1 as a Key Estrogen Receptor Regulatory Factor

Hisham Mohammed, Clive D'Santos, Aurelien A. Serandour, H. Raza Ali, Gordon D. Brown, Alan Atkins, Oscar M. Rueda, Kelly A. Holmes, Vasiliki Theodorou, Jessica L.L. Robinson, Wilbert Zwart, Amel Saadi, Caryn S. Ross-Innes, Suet Feung Chin, Suraj Menon, John Stingl, Carlo Palmieri, Carlos Caldas, Jason S. Carroll

Research output: Contribution to journalArticlepeer-review

248 Scopus citations


Estrogen receptor-α (ER) is the driving transcription factor in most breast cancers, and its associated proteins can influence drug response, but direct methods for identifying interacting proteins have been limited. We purified endogenous ER using an approach termed RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins) and discovered the interactome under agonist- and antagonist-liganded conditions in breast cancer cells, revealing transcriptional networks in breast cancer. The most estrogen-enriched ER interactor is GREB1, a potential clinical biomarker with no known function. GREB1 is shown to be a chromatin-bound ER coactivator and is essential for ER-mediated transcription, because it stabilizes interactions between ER and additional cofactors. We show a GREB1-ER interaction in three xenograft tumors, and using a directed protein-protein approach, we find GREB1-ER interactions in half of ER+ primary breast cancers. This finding is supported by histological expression of GREB1, which shows that GREB1 is expressed in half of ER+ cancers, and predicts good clinical outcome. These findings reveal an unexpected role for GREB1 as an estrogen-specific ER cofactor that is expressed in drug-sensitive contexts.

Original languageEnglish (US)
Pages (from-to)342-349
Number of pages8
JournalCell Reports
Issue number2
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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