Mechanisms of Signal Transduction
COMMD Proteins, a Novel Family of Structural and Functional Homologs of MURR1*

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MURR1 is a multifunctional protein that inhibits nuclear factor κB (NF-κB), a transcription factor with pleiotropic functions affecting innate and adaptive immunity, apoptosis, cell cycle regulation, and oncogenesis. Here we report the discovery of a new family of proteins with homology to MURR1. These proteins form multimeric complexes and were identified in a biochemical screen for MURR1-associated factors. The family is defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions. Like MURR1, several of these factors also associate with and inhibit NF-κB. The proteins designated as COMMD or COMM domain containing 1–10 are extensively conserved in multicellular eukaryotic organisms and define a novel family of structural and functional homologs of MURR1. The prototype of this family, MURR1/COMMD1, suppresses NF-κB not by affecting nuclear translocation or binding of NF-κB to cognate motifs; rather, it functions in the nucleus by affecting the association of NF-κB with chromatin.

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This work was supported in part by the University of Michigan Biological Scholars Program, Department of Defense Idea Award PC040215 and National Institutes of Health Grant GM067827 (to C. S. D.), by an American Gastroenterological Association Research Scholar Award, a Merit Review Entry Program Award, and a Veterans Education and Research Association of Michigan Award (to E. B.), by NCI, National Institutes of Health Grants K01CA78595, R01CA104397, and R01CA095644 (to M. W. M.), and by T32 CA09676 (to J. C. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental figure and table.