COMMD1: a novel protein involved in the proteolysis of proteins

COMMD1 is a protein which is associated with multiple cellular pathways, including NFkappaB signaling, copper homeostasis and sodium transport. Recently we found that COMMD1 is also essential for normal mouse embryogenesis. Embryos deficient for Commd1 are retarded and die between 9.5 and 10.5 dpc. Increased HIF-1 activity and elevated HIF-1alpha protein expression were observed in 9.5 dpc Commd1-deficient embryos. In line with these in vivo data, in vitro studies showed that reduced COMMD1 expression caused increased HIF-1alpha protein stability and HIF-1 activity. Functional characterization of COMMD1 in NFkappaB signaling and ATP7B-dependent biliary copper excretion suggested that COMMD1 also has a role in regulating the protein degradation of RelA (p65) and ATP7B. The exact function of COMMD1 in these pathways remains elusive but these recent studies suggest that COMMD1 is associated with the ubiquitin-proteasomal system for regulating protein stability.