The SUD1 gene encodes a putative E3 ubiquitin ligase and is a positive regulator of 3-hydroxy-3-methylglutaryl coenzyme a reductase activity in Arabidopsis

The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme catalyzes the major rate-limiting step of the mevalonic acid (MVA) pathway from which sterols and other isoprenoids are synthesized. In contrast with our extensive knowledge of the regulation of HMGR in yeast and animals, little is known about this process in plants. To identify regulatory components of the MVA pathway in plants, we performed a genetic screen for second-site suppressor mutations of the Arabidopsis thaliana highly drought-sensitive drought hypersensitive2 (dry2) mutant that shows decreased squalene epoxidase activity. We show that mutations in SUPPRESSOR OF DRY2 DEFECTS1 (SUD1) gene recover most developmental defects in dry2 through changes in HMGR activity. SUD1 encodes a putative E3 ubiquitin ligase that shows sequence and structural similarity to yeast Degradation of α factor (Doα10) and human TEB4, components of the endoplasmic reticulum–associated degradation C (ERAD-C) pathway. While in yeast and animals, the alternative ERAD-L/ERAD-M pathway regulates HMGR activity by controlling protein stability, SUD1 regulates HMGR activity without apparent changes in protein content. These results highlight similarities, as well as important mechanistic differences, among the components involved in HMGR regulation in plants, yeast, and animals.This work was supported by grants from Ministerio de Ciencia e Innovación (cofinanced by the European Regional Development Fund) to M.A.B. (BIO2011-23859 and CSD2007-00057), A.F. (BIO2009-06984 and CSD2007-00036), and O.B. from Universidad de la República-Comisión Sectorial de Investigación Científica (Grupo 418). V.G.D. was supported by a Formación del Personal Investigador fellowship from Ministerio de Educación y Ciencia (BIO2005-04733), and V.A.-S. was supported by FundaçÃo para a Ciência e a Tecnologia (FCT) (Grant SFRH/BD/38583/2007).Peer reviewe