Sterol regulatory element–binding proteins (SREBPs) are basic helix-loop-helix–leucine zipper transcription factors, including SREBP-1 and SREBP-2. SREBP-1 is synthesized as a precursor that is attached to the nuclear envelope and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription by binding to the SRE1. Sterols inhibit the cleavage of the precursor, and the mature nuclear form is rapidly catabolized, thereby reducing transcription.Among the isoforms of SREBPs, SREBP-1c activates all lipogenic genes in the liver. Phosphorylation of SREBP-1c at Ser372 by AMPK ihibits the proteolytic cleavage of SREBP-1c and therefore suppresses the expression of its target genes in the liver.
