title: COMMD proteins, a novel family of structural and functional homologs of MURR1.
abstract: MURR1 is a multifunctional protein that inhibits nuclear factor kappaB (NF-kappaB), 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-kappaB. 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-kappaB not by affecting nuclear translocation or binding of NF-kappaB to cognate motifs; rather, it functions in the nucleus by affecting the association of NF-kappaB with chromatin.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
authors.forename: Ezra
authors.initials: E
authors.lastname: Burstein
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Hoberg
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Wilkinson
authors.forename: Julie M
authors.initials: JM
authors.lastname: Rumble
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Csomos
authors.forename: Christine M
authors.initials: CM
authors.lastname: Komarck
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Maine
authors.forename: John C
authors.initials: JC
authors.lastname: Wilkinson
authors.forename: Marty W
authors.initials: MW
authors.lastname: Mayo
authors.forename: Colin S
authors.initials: CS
authors.lastname: Duckett
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins; D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C480519:COMMD1 protein, human; D002352:Carrier Proteins; D002843:Chromatin; D016328:NF-kappa B; D011506:Proteins; D008156:Luciferases; D005982:Glutathione Transferase