Protein Quality Control as a Strategy for Cellular Regulation: Lessons from Ubiquitin-Mediated Regulation of the Sterol Pathway

A study was conducted to demonstrate the use of protein quality control for cellular regulation. The study was focused on the regulated degradation of yeast HMGR and the use of cellular quality control. The stability of HMGR decreased with the addition of seterol precursors or sterols were added to cell culture medium for a mammalian cells, which further showed that the stability of HMGR was depended on feedback regulation. It was observed during the study that N-terminal multispanning domain mediated regulated degradation of the HMGR molecule, which allowed the replacement of the C-terminal catalytic region with enzymatic or optical reporters. The mechanism of regulated HMGR degradation in yeast and in general was examined using genetic analysis and it was found that the HRD genes were responsible for Hmg-CoA reductase degradation.