Sterol-induced degradation of HMG CoA reductase depends on interplay of two Insigs and two ubiquitin ligases, gp78 and Trc8.

@article{Jo2011SterolinducedDO,
  title={Sterol-induced degradation of HMG CoA reductase depends on interplay of two Insigs and two ubiquitin ligases, gp78 and Trc8.},
  author={Youngah Jo and Peter Chang-whan Lee and Peter V. Sguigna and Russell A. DeBose-Boyd},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2011},
  volume={108 51},
  pages={
          20503-8
        }
}
Accumulation of sterols in membranes of the endoplasmic reticulum (ER) leads to the accelerated ubiquitination and proteasomal degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a rate-limiting enzyme in synthesis of cholesterol and nonsterol isoprenoids. This degradation results from sterol-induced binding of reductase to the Insig-1 or Insig-2 proteins of ER membranes. We previously reported that in immortalized human fibroblasts (SV-589 cells) Insig-1, but not Insig-2, recruits… CONTINUE READING
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