Resumen de Characterization of second-site mutations of the arabidopsis thaliana sterol biosynthesis mutant dry2 highlight a role of erad in the regulation of hmgr activity
This thesis identifies essential differences in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), the rate-limiting enzyme of the mevalonic acid (MVA) pathway from which isoprenoids and sterols are synthesized, between yeast or animals and plants. In order to identify new regulatory components of the MVA pathway in Arabidopsis are defined the objectives: (i) isolation and characterization of second-site mutations that suppress the developmental phenotype of the sterol mutant dry2; (ii) identification of the suppressor gene(s) by map-based cloning; and (iii) structural, phylogenetic and functional characterization of the gene identified.
The results reported that mutations in SUD1, which encodes an ERAD E3 ubiquitin ligase with homology to yeast Doa10 and human TEB4, recover most of the developmental defects of dry2 through an ERAD-dependent regulation of HMGR activity. However, while in yeasts and animals the HMGR regulation occurs by controlling the protein stability through the HRD pathway, the regulation of HMGR in plants by SUD1 is exerted at the activity level by the alternative ERAD Doa10 pathway. Thus, the results identify common elements but mechanistic differences in HMGR regulation between plants, yeast and animals.
