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 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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Binding Sites
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CCAAT-Enhancer-Binding Proteins*
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Cell Nucleus / metabolism
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Cloning, Molecular
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DNA Primers
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DNA, Complementary / metabolism
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / isolation & purification
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation*
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HeLa Cells
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Helix-Loop-Helix Motifs*
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Humans
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Leucine Zippers*
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Molecular Sequence Data
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / isolation & purification
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Nuclear Proteins / metabolism*
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RNA, Messenger / biosynthesis
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RNA, Messenger / metabolism
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Receptors, LDL / biosynthesis*
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Receptors, LDL / genetics*
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / metabolism
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Regulatory Sequences, Nucleic Acid*
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Repetitive Sequences, Nucleic Acid
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Sequence Homology, Amino Acid
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Sterol Regulatory Element Binding Protein 1
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Transcription Factors*
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Transcription, Genetic
Substances
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CCAAT-Enhancer-Binding Proteins
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DNA Primers
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DNA, Complementary
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DNA-Binding Proteins
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Nuclear Proteins
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RNA, Messenger
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Receptors, LDL
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Recombinant Proteins
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SREBF1 protein, human
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Sterol Regulatory Element Binding Protein 1
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Transcription Factors
Associated data
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GENBANK/L20888
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GENBANK/L20889
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GENBANK/L26083
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GENBANK/L33709
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GENBANK/S60904
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GENBANK/S60905
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GENBANK/S60924
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GENBANK/S66167
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GENBANK/S66168
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GENBANK/U00968