SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein.
The sterol regulatory element binding proteins (SREBP-1 and -2) activate transcription of genes whose products are involved in the cellular uptake and synthesis of cholesterol. Although considerable effort has been exerted to define the events regulating the levels of active SREBP, little is known about the transcriptional cofactors mediating SREBP function. In an unbiased search for potential coactivators of SREBP, we isolated a protein of 265 kD from HeLa cells that directly bound SREBP-1 and SREBP-2. Peptide sequencing and Western blot analysis established that the 265-kD protein was CBP (CREB-binding protein), a recently identified transcriptional coactivator. The putative activation domain of SREBP was shown to bind specifically to amino-terminal domains of recombinant CBP and p300 (a CBP-related protein). Moreover, transfection studies demonstrated that CBP enhances the ability of SREBP to activate transcription of reporter genes in HeLa cells. Together, these data suggest that CBP mediates SREBP transcriptional activity, thus revealing a new step in the biochemical pathway regulating cholesterol metabolism.
Oliner
J D
JD
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley 94720-3204, USA.
Andresen
J M
JM
Hansen
S K
SK
Zhou
S
S
Tjian
R
R
D000818:Animals; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D050882:CREB-Binding Protein; D002467:Cell Nucleus / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila; D004926:Escherichia coli / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D017421:Sequence Analysis; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D015534:Trans-Activators; D014157:Transcription Factors; D002784:Cholesterol; D050882:CREB-Binding Protein; C494363:CREBBP protein, human