COMMD proteins and the control of the NF kappa B pathway.
The COMM domain containing (COMMD) family of proteins represents a recently discovered set of evolutionarily conserved factors characterized by the presence of a defining carboxy-terminal motif. In vertebrates, there are ten members of the family, and among their emerging functions the control of the transcription factor NFkappaB has been most extensively studied. NFkappaB plays a critical role in a number of homeostatic processes in multicellular organisms, including the regulation of immunity and cell survival. COMMD proteins inhibit NFkappaB mediated gene expression, and recent mechanistic studies have revealed that COMMD1 controls the ubiquitination of NFkappaB subunits, an event linked to transcriptional termination. COMMD1 binds to a multimeric ubiquitin ligase containing Elongins B/C, Cul2 and SOCS1 (ECS( SOCS1)). In this complex, COMMD1 facilitates the binding of NFkappaB subunits to the ligase, thereby promoting their ubiquitination and degradation. Additional insights gained from these studies indicate that COMMD proteins likely play a broader role in cellular homeostasis through their participation in the ubiquitination pathway.
Maine
Gabriel N
GN
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Burstein
Ezra
E
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle / Q000502:physiology; D006801:Humans; D005810:Multigene Family; D016328:NF-kappa B / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C480519:COMMD1 protein, human; D002352:Carrier Proteins; D016328:NF-kappa B; D011506:Proteins