Ubiquitin ligase gp78 increases solubility and facilitates degradation of the Z variant of α- 1 -antitrypsin

α - 1 - antitrypsin （AAT） is the most abundant circulating serine proteinase inhibitor of the serpin superfamily. Deficiency of circulating AAT is the most widely recognized abnormality of a proteinase inhibitor that causes lung disease. AAT deficiency is caused by mutations of the AAT gene that lead to AAT protein retention in the endoplasmic reticulum （ER）. Moreover, the mutant AAT accumulated in the ER predisposes the homozygote to severe liver injuries, such as neonatal hepatitis, juvenile cirrhosis, and hepatocellular carcinoma. Despite the fact that mutant AAT protein is subject to Erassociated degradation we report that gp78, a ubiquitin ligase （E3） pairing with mammalian Ubc7 for ERAD, ubiquitinates and facilitates degradation of ATZ. the classic deficiency variant of AAT having a Z mutation （Glu342Lys）.