Ubiquitin receptor found

have identified an endosomal receptor complex that pushes proteins into the lumen of endosomes destined for the vacuole. This internalization step represents another possible site of regulation for controlling receptor activity. Receptors and other plasma membrane proteins bound for destruction are tagged with one or more ubiquitin (Ub) molecules before they are internalized in vesicles that fuse with early endosomes. To be fully degraded when the endosome fuses with the vacuole, the tagged proteins must bud off a second time to form a multivesiculated body (MVB)—a structure that has vesicles inside the lumen of the endosome. Proteins that escape this step never reach the inside of the vacuole and may still be recycled back to the cell surface. It turns out that Ub is a potent sorting signal for the incorporation of proteins into the lumenal vesicles of the MVB. With the new results, the authors have identified the protein Hse1p, P Securin correct separation he separation of sister chromatids at anaphase cannot commence until separase cleaves the cohesin subunit Scc1. Separase is regulated by an inhibitor, securin, that seems to have contradictory character-istics—it prevents Scc1 cleavage by separase, yet at the same time it is required for separase function and correct chromatid separation. Institute, London), and colleagues explain how securin primes separase for a rapid burst of activity in mitosis. To promote correct separase function, securin first ensures the nuclear localization of separase. Securin levels normally drop during anaphase and do not increase again until S phase. When the group expressed securin in G1, they found it increased the amount of separase found in the nucleus. But just bringing separase to the nucleus was not enough; securin also acted as a chaperone for separase to achieve the preferred conformation for its protease activity. Separase extracted from cells that contained securin in the previous cell cycle was more active than separase from cells lacking securin. While securin promotes separase activity, it also has two tricks to ensure that the protease does not cleave cohesin until the time is right. " Securin uses a foolproof twofold mechanism, " says Uhlmann. " It prevents separase from activating itself and at the same time prevents it from binding to its target substrate. " The group found that interaction of separase NH 2-terminal and protease domains is crucial for the protease activity. Securin interacted with both domains, disrupting separase self-contact. Securin also prevented separase …