Human BRE1 is an E3 ubiquitin ligase for Ebp1 tumor suppressor

Zhixue Liu, Sang Muk Oh, Masashi Okada, Xia Liu, Dongmei Cheng, Junmin Peng, Daniel J. Brat, Shi Yong Sun, Wei Zhou, Wei Gu, Keqiang Ye*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Human Brel, an E3 ligase for H2B monoubiquitination, binds p53 and enhances activator-dependent transcription. Ebpl n ErbB3 receptor-binding protein, inhibits cell proliferation and acts as a tumor suppressor. Here, we show that hBrel cts as an E3 ubiquitin ligase for Ebpl tumor suppressor and promotes its polyubiquitination and degradation. Ebpl is olyubiquitinated in cancer cells, which is regulated by its phosphorylation. We identified hBrel acting as an E3 ligasefor Ebpl and increasing its polyubiquitination. Depletion of hBrel blocks Ebpl's polyubiquitination and elevates its rotein level, preventing cancer proliferation. hBrel binds Ebpl and suppresses its repressive effect on E2F-l. Moreover, bpl protein level is substantially diminished in human cancers. It is robustly phosphorylated and localized in thenucleus of primary gliomas, correlating with hBrel subcellular residency. Thus, hBrel inhibits Ebpl's tumor suppressiveactivity through mediating its polyubiquitination and degradation.

Original languageEnglish (US)
Pages (from-to)757-768
Number of pages12
JournalMolecular Biology of the Cell
Volume20
Issue number3
DOIs
StatePublished - Jan 1 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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