Abstract
Sterol regulatory element 1 (SRE-1), a decamer (5'-ATC-ACCCCAC-3') flanking the low density lipoprotein (LDL) receptor gene, activates transcription in sterol-depleted cells and is silenced by sterols. We report the cDNA cloning of human SREBP-1, a protein that binds SRE-1, activates transcription, and thereby mediates the final regulatory step in LDL metabolism. SREBP-1 contains a basic-helix-loop-helix-leucine zipper (bHLH-ZIP) motif, but it differs from other bHLH-ZIP proteins in its larger size (1147 amino acids) and target sequence. Instead of an inverted repeat (CANNTG), the target for all known bHLH-ZIP proteins, SRE-1 contains a direct repeat of CAC. Overexpression of SREBP-1 activates transcription of reporter genes containing SRE-1 in the absence (15-fold) and presence (90-fold) of sterols, abolishing sterol regulation. We suggest that SREBP-1 is regulated by an unknown factor that is overwhelmed when SREBP-1 is overexpressed. Understanding the regulation of SREBP-1 may be crucial for understanding the control of plasma cholesterol in humans.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
