| First Author | Kim ST | Year | 2018 |
| Journal | J Cell Sci | Volume | 131 |
| Issue | 17 | PubMed ID | 30111582 |
| Mgi Jnum | J:266925 | Mgi Id | MGI:6200492 |
| Doi | 10.1242/jcs.217646 | Citation | Kim ST, et al. (2018) The N-recognin UBR4 of the N-end rule pathway is targeted to and required for the biogenesis of the early endosome. J Cell Sci 131(17):jcs217646 |
| abstractText | The N-end rule pathway is a proteolytic system in which single N-terminal residues of proteins act as N-degrons. These degrons are recognized by N-recognins, facilitating substrate degradation via the ubiquitin (Ub) proteasome system (UPS) or autophagy. We have previously identified a set of N-recognins [UBR1, UBR2, UBR4 (also known as p600) and UBR5 (also known as EDD)] that bind N-degrons through their UBR boxes to promote proteolysis by the proteasome. Here, we show that the 570 kDa N-recognin UBR4 is associated with maturing endosomes through an interaction with Ca(2+)-bound calmodulin. The endosomal recruitment of UBR4 is essential for the biogenesis of early endosomes (EEs) and endosome-related processes, such as the trafficking of endocytosed protein cargos and degradation of extracellular cargos by endosomal hydrolases. In mouse embryos, UBR4 marks and plays a role in the endosome-lysosome pathway that mediates the heterophagic proteolysis of endocytosed maternal proteins into amino acids. By screening 9591 drugs through the DrugBank database, we identify picolinic acid as a putative ligand for UBR4 that inhibits the biogenesis of EEs. Our results suggest that UBR4 is an essential modulator in the endosome-lysosome system.This article has an associated First Person interview with the first author of the paper. |
