Studies On RNF186,A Ubiquitin E3Ligase With A Ring Domain

The ubiquitination of proteins plays an important role in regulating many cellular and organismal processes. Ub conjugation to the target protein via an isopeptide bound between its C-terminal glycine and the lysine residue of the substrate involves a cascade of enzymatic reactions. E3ligases play central regulatory roles in the ubiquitination cascade reactions. There are two major types of E3ligases in eukaryotic cells:HECT E3s and ringer finger E3s defined by the presence of their specific E2recruiting domains. RING finger E3s are the most numerous and about616members have been discovered in human cells up to now.ER is a very important organelle involved in many essential cellular processes which are required for cell survival. Most importantly of these processes are protein modification, sorting and transportation. In eukaryotic cells, proteins enter the ER as unfolded polypeptide, only after they snap into the right conformation,these secreted and transmembrane proteins can be transported to the destination. Cells have evolved a precise system to adjust the protein-folding capacity in order to adapt different environment stress. Such strict regulation is achieved through intracellular signaling pathway which named unfolded protein response(UPR). Disturbance in the ER calcium regulation is one of the stress signals because the high calcium concentration in the ER is necessary for protein folding. Bcl-2family on guard at the ER can regulate the release of calcium into the cytosol from ER.BNip proteins are a pro-apoptotic subgroup of Bcl-2family, which have a conserved BH3domain. The BNip group of proteins include BNipl, BNip2, BNip3and Nix in humans. BNipl is a228amino acid protein and has a carboxyl terminal transmembrane (TM) domain which enable it to localize in ER. Some previous papers reported that BNip1played a role in induction of apoptosis, maintaining the integrity of the ER network and mitochondrial fragmentation. Here we demonstrate that one ring finger E3RNF186plays a important role in regulating ER stress associated apoptosis by interacting with BNipl.