The N-recognin UBR4 of the N-end rule pathway is targeted to and required for the biogenesis of the early endosome

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The N-recognin UBR4 of the N-end rule pathway is targeted to and required for the biogenesis of the early endosome
S T Kim; Y J Lee; T Tasaki; S R Mun; Joonsung Hwang; M J Kang; S Ganipisetti; E C Yi; Bo Yeon Kim; Y T Kwon
Bibliographic Citation
Journal of Cell Science, vol. 131, no. 7, pp. 217646-217646
Publication Year
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 Ca2+-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.
AutophagyEndosomeN-terminal arginylationUBR boxUbiquitin-proteasome system
Company Biologists Ltd
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Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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