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The Journal of Biological Chemistry

Year: 2009  |  Volume: 284  |  Issue: 24  |  Page No.: 16135 - 16145

OTU Domain-containing Ubiquitin Aldehyde-binding Protein 1 (OTUB1) Deubiquitinates Estrogen Receptor (ER) {alpha} and Affects ER{alpha} Transcriptional Activity

V Stanisic, A Malovannaya, J Qin, D. M Lonard and B. W. O`Malley

Abstract

Estrogen receptor (ER) is an essential component in human physiology and is a key factor involved in the development of breast and endometrial cancers. ER protein levels and transcriptional activity are tightly controlled by the ubiquitin proteasome system. Deubiquitinating enzymes, a class of proteases capable of removing ubiquitin from proteins, are increasingly being seen as key modulators of the ubiquitin proteasome system, regulating protein stability and other functions by countering the actions of ubiquitin ligases. Using mass spectrometry analysis of an ER protein complex, we identified OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) as a novel ER-interacting protein capable of deubiquitinating ER in cells and in vitro. We show that OTUB1 negatively regulates transcription mediated by ER in transient reporter gene assays and transcription mediated by endogenous ER in Ishikawa endometrial cancer cells. We also show that OTUB1 regulates the availability and functional activity of ER in Ishikawa cells by affecting the transcription of the ER gene and by stabilizing the ER protein in the chromatin.

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