TY - JOUR
T1 - SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene
AU - Yokoyama, Chieko
AU - Wang, Xiaodong
AU - Briggs, Michael R.
AU - Admon, Arie
AU - Wu, Jian
AU - Hua, Xianxin
AU - Goldstein, Joseph L.
AU - Brown, Michael S.
N1 - Funding Information:
We thank Robert Tjian and Steve McKnight for helpful suggestions; Jeff Cormier and Amber Luong for DNA sequencing; Gloria Brunschede and Daphne Norsworthy for excellent technical assistance; Lavon Sanders and Edith Womack for invaluable help with tissue culture; and our colleagues Mark Evans, Ryuichiro Sato, and Jianxin Yang for sharing unpublished data on the hamster SREBP-1 cDNA sequence. This research is supported by grants from the National Institutes of Health (NIH) (HL-20948) and the Perot Family Foundation. X. W. is the recipient of a postdoctoral fellowship from the Damon Runyon-Walter Winchell Cancer Research Fund (#1156). M. R. B. was the recipient of a postdoctoral fellowship from NIH (5F32HL07863).
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(05)80095-9
DO - 10.1016/S0092-8674(05)80095-9
M3 - Article
C2 - 8402897
AN - SCOPUS:0027490174
VL - 75
SP - 187
EP - 197
JO - Cell
JF - Cell
SN - 0092-8674
IS - 1
ER -