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
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.