2. Academic Validation
  3. Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex

Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex

  • EMBO J. 2002 Feb 1;21(3):355-64. doi: 10.1093/emboj/21.3.355.
Thomas K Albert 1,  Hiroyuki Hanzawa,  Yvonne I A Legtenberg,  Marjolein J de Ruwe,  Fiona A J van den Heuvel,  Martine A Collart,  Rolf Boelens,  H Th Marc Timmers
Affiliations

Affiliation

  • 1 Laboratory for Physiological Chemistry, University Medical Center, 3508 AB Utrecht, The Netherlands.
PMID: 11823428 DOI: 10.1093/emboj/21.3.355
Abstract

The RING finger protein CNOT4 is a component of the CCR4-NOT complex. This complex is implicated in repression of RNA polymerase II transcription. Here we demonstrate that CNOT4 functions as a ubiquitin-protein ligase (E3). We show that the unique C4C4 RING domain of CNOT4 interacts with a subset of ubiquitin-conjugating enzymes (E2s). Using NMR spectroscopy, we detail the interaction of CNOT4 with UbcH5B and characterize RING residues that are critical for this interaction. CNOT4 acts as a potent E3 ligase in vitro. Mutations that destabilize the E2-E3 interface abolish this activity. Based on these results, we present a model of how E3 ligase function within the CCR4-NOT complex relates to transcriptional regulation.

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