Rot1 is degraded by ERAD: new insights into protein homeostasis of an essential gene

Abstract

Rot1, an essential type-I ER (endoplasmic reticulum) membrane protein, is implicated in diverse functions as -1,6 glycan synthesis, actin cytoskeleton polarization dynamics, lysis of autophagic bodies and most importantly as a molecular chaperone [1-4]. For these varied roles, Rot1p adopts an unusual topology whereby the Nterminus, which gets glycosylated, faces the ER lumen and its single hydrophobic Cterminus with its essential serine-250 residue enables cell survivability [5, 6]. In addition, a comprehensive geneticinteraction analysis suggested its interaction with the proteasomal system. Whilst its diverse functions have been extensively studied; the dynamics of Rot1 protein stability in yeast cells is unknown. In this issue, Juanes et.al., [doi.org/cg8p] showed that the Rot1 protein stability is mediated by the ubiquitin proteasome system (UPS), which is dependent on the main degradation pathway located at the ER, the ER-associated degradation system (ERAD). Here the authors employed the GAL4 shut-off assay to ascertain the role of the ERAD system, Ubc6, Ubc7 and Hrd1, along with Pre1 and Pre2 of the UPS on Rot1 protein stability.