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

Chieko Yokoyama, Xiaodong Wang, Michael R. Briggs, Arie Admon, Jian Wu, Xianxin Hua, Joseph L. Goldstein, Michael S. Brown

Research output: Contribution to journalArticle

725 Scopus citations

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 mediate 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.

Original languageEnglish (US)
Pages (from-to)187-197
Number of pages11
JournalCell
Volume75
Issue number1
DOIs
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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