HSCARG regulates NF-kappaB activation by promoting the ubiquitination of RelA or COMMD1.

ABSTRACT: The redox sensor protein HSCARG translocates from the cytoplasm to the nucleus in response to decreased cellular NADPH or increased nitric oxide, and is involved in protein regulation. However, the regulatory mechanism of HSCARG has remained elusive. In this report, through a yeast two-hybrid screen, HSCARG was found to associate with the copper metabolism gene MURR1 domain containing protein 1 (COMMD1), an inhibitor of NF-kappaB, and negatively regulate COMMD1 by accelerating its ubiquitination and proteasome-dependent degradation. Interestingly, we observed that HSCARG also blocked basal and stimulus-coupled NF-kappaB activation by promoting ubiquitination and degradation of the NF-kappaB subunit RelA. Further analyses showed that in cells under normal conditions, HSCARG localized mainly

SUBMITTER: Lian M 

PROVIDER: S-EPMC2709395 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature