Open AccessUBIQUITIN AND THE CONTROL OF PROTEIN FATE IN THE SECRETORY AND ENDOCYTIC PATHWAYS
Author(s) -
Juan S. Bonifacino,
Allan M. Weissman
Publication year - 1998
Publication title -
annual review of cell and developmental biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.094
H-Index - 220
eISSN - 1530-8995
pISSN - 1081-0706
DOI - 10.1146/annurev.cellbio.14.1.19
Subject(s) - ubiquitin , microbiology and biotechnology , endoplasmic reticulum , biology , internalization , cytosol , proteasome , transmembrane protein , endocytic cycle , endoplasmic reticulum associated protein degradation , membrane protein , f box protein , protein degradation , ubiquitins , ubiquitin ligase , biochemistry , endocytosis , receptor , unfolded protein response , membrane , enzyme , gene
The modification of proteins by chains of ubiquitin has long been known to mediate targeting of cytosolic and nuclear proteins for degradation by proteasomes. In this article, we discuss recent developments that reveal the involvement of ubiquitin in the degradation of proteins retained within the endoplasmic reticulum (ER) and in the internalization of plasma membrane proteins. Both luminal and transmembrane proteins retained in the ER are now known to be retrotranslocated into the cytosol in a process that involves ER chaperones and components of the protein import machinery. Once exposed to the cytosolic milieu, retro-translocated proteins are degraded by the proteasome, in most cases following polyubiquitination. There is growing evidence that both the ubiquitin-conjugating machinery and proteasomes may be associated with the cytosolic face of the ER membrane and that they could be functionally coupled to the process of retrotranslocation. The ubiquitination of plasma membrane proteins, on the other hand, mediates internalization of the proteins, which in most cases is followed by lysosomal/vacuolar degradation. There is, however, a well-documented case of a plasma membrane protein (the c-Met receptor) for which ubiquitination results in proteasomal degradation. These recent findings imply that ubiquitin plays more diverse roles in the regulation of the fate of cellular proteins than originally anticipated.