COMMD1 expression is controlled by critical residues that determine XIAP binding

Gabriel N. Maine, Xicheng Mao, Patricia A. Muller, Christine M. Komarck, Leo W J Klomp, Ezra Burstein

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

COMMD {COMM [copper metabolism Murr1 (mouse U2af1-rs1 region 1)] domain-containing} proteins participate in several cellular processes, ranging from NF-κB (nuclear factor κB) regulation, copper homoeostasis, sodium transport and adaptation to hypoxia. The best-studied member of this family is COMMD1, but relatively little is known about its regulation, except that XIAP [X-linked IAP (inhibitor of apoptosis)] functions as its ubiquitin ligase. In the present study, we identified that the COMM domain of COMMD1 is required for its interaction with XIAP, and other COMMD proteins can similarly interact with IAPs. Two conserved leucine repeats within the COMM domain were found to be critically required for XIAP binding. A COMMD1 mutant which was unable to bind to XIAP demonstrated a complete loss of basal ubiquitination and great stabilization of the protein. Underscoring the importance of IAP-mediated ubiquitination, we found that long-term expression of wild-typeCOMMD1 results in nearly physiological protein levels as a result of increased ubiquitination, but this regulatory event is circumvented when a mutant form that cannot bind XIAP is expressed. In summary, our findings indicate that COMMD1 expression is controlled primarily by protein ubiquitination, and its interaction with IAP proteins plays an essential role.

Original languageEnglish (US)
Pages (from-to)601-609
Number of pages9
JournalBiochemical Journal
Volume417
Issue number2
DOIs
StatePublished - Jan 15 2009

Keywords

  • Copper metabolism Murr1 (mouse U2af1-rs1 region) domain-containing (COMMD) protein
  • Inhibitor of apoptosis (IAP)
  • Ubiquitin
  • X-linked inhibitor of apoptosis (XIAP)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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