SREBP proteolytic cleavage

SREBP resides in the endoplasmic reticulum, where it is bound to SCAP by its regulatory (Reg) domain. When cholesterol levels fall, SCAP and SREBP move to the Golgi complex, where SREBP undergoes successive proteolytic cleavages by a serine protease and a metalloprotease. The released DNA-binding domain moves to the nucleus to alter gene expression. [After an illustration provided by Dr. Michael Brown and Dr. Joseph Goldstein.]... 

Fig. 1.2 A schematic overview of the proteolytic processing of SREBPs. This pathway was described as a cholesterol-sensing process which applies to both SREBP-2 and SREBP-la. While SCAP and Insig are involved in the proteolytic cleavage of SREBP-lc the detailed mechanisms by which insulin regulates SREBP-lc processing are not known...

Sterol-response element-binding proteins (SREBPs) are transcription factors that coor-dinately increase the synthesis of fatty acids and cholesterol (Chapters 6, 7, and 14). The transcriptionally active forms of SREBPs are generated from precursor proteins by a sterol-dependent proteolytic cleavage [8]. Several studies have indicated that an increased production of transcriptionally active SREBPs stimulates VLDL secretion. 

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