HMGCR-dependent SREBP1a maturation (simplified scheme). 1a, mature SREBP1a protein; ER, endoplasmic reticulum. (see section »PXR versus LXR«)

The dogma of the SREBP1 protein:

»Sterols inhibit the cleavage of the precursor, and the mature nuclear form is rapidly catabolized, thereby reducing transcription.« (see ref 1, ref 2, ref 3)

However, with all due respect, I would like to mention that the results of dozens of scientific articles contradict and/or do not support this dogma. The literature analysis on srebp1a.com and the results of the following mentioned article reveal it.

Hwang et al. Contribution of Accelerated Degradation to Feedback Regulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase and Cholesterol Metabolism in the Liver. J Biol Chem. 2016 Jun 24;291(26):13479-94.

Before the literature analysis on srebp1a.com and the analysis of the article mentioned above, please consider the following two points:

1. HMGCR is the rate-limiting enzyme of sterol biosynthesis.

2. HMGCR protein/activity induces the maturation of SREBP1.