Identification of a zinc finger protein that binds to the sterol regulatory element.
Cholesterol balance in mammalian cells is maintained in part by sterol-mediated repression of gene transcription for the low density lipoprotein receptor and enzymes in the cholesterol biosynthetic pathway. A promoter sequence termed the sterol regulatory element (SRE) is essential for this repression. With the use of an oligonucleotide containing the SRE to screen a human hepatoma complementary DNA expression library, a clone for a DNA binding protein was isolated that binds to the conserved SRE octanucleotide in both a sequence-specific and a single-strand--specific manner. This protein contains seven highly conserved zinc finger repeats that exhibit striking sequence similarity to retroviral nucleic acid binding proteins (NBPs). We have designated the protein "cellular NBP" (CNBP). CNBP is expressed in a wide variety of tissues, is up regulated by sterols, and exhibits binding specificity that correlates with in vivo function. These properties are consistent with a role in sterol-mediated control of transcription.
Rajavashisth
T B
TB
Department of Medicine, University of California, Los Angeles 90024.
Taylor
A K
AK
Andalibi
A
A
Svenson
K L
KL
Lusis
A J
AJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism*; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D008113:Liver Neoplasms / Q000378:metabolism; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins; D011973:Receptors, LDL / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D013261:Sterols / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C433227:CNBP protein, human; D015342:DNA Probes; D004268:DNA-Binding Proteins; D008667:Metalloproteins; D016601:RNA-Binding Proteins; D011973:Receptors, LDL; D013261:Sterols; D004247:DNA; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases