Insig proteins regulate cholesterol homeostasis by acting as sensors and mediators that bind to SCAP and HMG-CoA reductase in diverse tissues and cultured cells.
This review elucidates the molecular mechanisms by which Insig proteins maintain cellular cholesterol homeostasis, highlighting their potential as therapeutic targets for hypercholesterolemia.
The molecular mechanism of how cells maintain cholesterol homeostasis has become clearer for the understanding of complicated association between sterol regulatory element-binding proteins (SREBPs), SREBP cleavage-activating protein (SCAP), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) and Insuin induced-genes (Insigs). The pioneering researches suggested that SREBP activated the transcription of genes encoding HMG-CoA reductase and all of the other enzymes involved in the synthesis of cholesterol and lipids. However, SREBPs can not exert their activities alone, they must form a complex with another protein, SCAP in the endoplasmic reticulum (ER) and translocate to Golgi. Insigs are sensors and mediators that regulate cholesterol homeostasis through binding to SCAP and HMG-CoA reductase in diverse tissues such as adipose tissue and liver, as well as the cultured cells. In this article, we aim to review on the dual functions of Insig protein family in cholesterol homeostasis.
Dong et al. (Sat,) conducted a review in Cholesterol homeostasis. Insig proteins was evaluated. Insig proteins regulate cholesterol homeostasis by acting as sensors and mediators that bind to SCAP and HMG-CoA reductase in diverse tissues and cultured cells.