Abstract
Sterol regulatory element 1 (SRE-1), a decamer (5′-ATCACCCCAC-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 187-197 |
| Number of pages | 11 |
| Journal | Cell |
| Volume | 75 |
| Issue number | 1 |
| State | Published - Oct 8 1993 |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
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SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. / Yokoyama, Chieko; Wang, Xiaodong; Briggs, Michael R.; Admon, Arie; Wu, Jian; Hua, Xianxin; Goldstein, Joseph L.; Brown, Michael S.
In: Cell, Vol. 75, No. 1, 08.10.1993, p. 187-197.Research output: Contribution to journal › Article
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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.
PY - 1993/10/8
Y1 - 1993/10/8
N2 - Sterol regulatory element 1 (SRE-1), a decamer (5′-ATCACCCCAC-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.
AB - Sterol regulatory element 1 (SRE-1), a decamer (5′-ATCACCCCAC-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.
UR - http://www.scopus.com/inward/record.url?scp=0027490174&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027490174&partnerID=8YFLogxK
M3 - Article
C2 - 8402897
AN - SCOPUS:0027490174
VL - 75
SP - 187
EP - 197
JO - Cell
JF - Cell
SN - 0092-8674
IS - 1
ER -