SREBP TRANSCRIPTIONAL ACTIVITY IS MEDIATED THROUGH AN INTERACTION WITH THE CREB-BINDING PROTEIN

Citation
Jd. Oliner et al., SREBP TRANSCRIPTIONAL ACTIVITY IS MEDIATED THROUGH AN INTERACTION WITH THE CREB-BINDING PROTEIN, Genes & development, 10(22), 1996, pp. 2903-2911
Citations number
55
Categorie Soggetti
Developmental Biology","Genetics & Heredity
Journal title
ISSN journal
08909369
Volume
10
Issue
22
Year of publication
1996
Pages
2903 - 2911
Database
ISI
SICI code
0890-9369(1996)10:22<2903:STAIMT>2.0.ZU;2-8
Abstract
The sterol regulatory element binding proteins (SREBP-1 and -2) activa te 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 SREB P, 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 SR EBP-1 and SREBP-2. Peptide sequencing and Western blot analysis establ ished that the 265-kD protein was CBP (CREB-binding protein), a recent ly identified transcriptional coactivator. The putative activation dom ain of SREBP was shown to bind specifically to amino-terminal domains of recombinant CBP and p300 (a CBP-related protein). Moreover, transfe ction studies demonstrated that CBP enhances the ability of SREBP to a ctivate transcription of reporter genes in HeLa cells. Together, these data suggest that CBP mediates SREBP transcriptional activity, thus r evealing a new step in the biochemical pathway regulating cholesterol metabolism.