SREBP-1, A BASIC-HELIX-LOOP-HELIX-LEUCINE ZIPPER PROTEIN THAT CONTROLS TRANSCRIPTION OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE

被引：548

作者：

YOKOYAMA, C ^{[1
]}

WANG, XD ^{[1
]}

BRIGGS, MR ^{[1
]}

ADMON, A ^{[1
]}

WU, J ^{[1
]}

HUA, XX ^{[1
]}

GOLDSTEIN, JL ^{[1
]}

BROWN, MS ^{[1
]}

机构：

[1] UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,HOWARD HUGHES MED INST,BERKELEY,CA 94720

来源：

CELL | 1993年 / 75卷 / 01期

关键词：

D O I：

10.1016/S0092-8674(05)80095-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (I 147 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.

引用

页码：187 / 197

页数：11

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