The ubiquitin-proteosome pathway of protein degradation is one of the mechanisms that ensure the proper level of cellular proteins. The ubiquitin-like (UbL) and ubiquitin-associated (UBA) domain containing protein family is thought to be involved in proteosomal degradation. One such protein is CIP75, also known as ubiquilin-4, interacts with a number of proteins such as Ataxin-1 and Connexin-43, resulting in an increased rate of turnover of these proteins. Overexpression CIP75 led to a significant reduction of Connexin-43 half-life, with the opposite being observed in siRNA knockdown experiments. CIP75 contains an N-terminal UbL domain which is thought to interact with proteins of the 26S proteosome complex and a C-terminal UBA domain which appears to mediate its interaction with Connexin-75. At least three isoforms of CIP75 are known to exist.
