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    Cell. 1993 Oct 8;75(1):187-97.

    SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene.

    Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS.

    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.

    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.

    PMID: 8402897 [PubMed - indexed for MEDLINE]

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