Premium
Cooperative interactions between CBP and TORC2 confer selectivity to CREB target gene expression
Author(s) -
Ravnskjaer Kim,
Kester Henri,
Liu Yi,
Zhang Xinmin,
Lee Dong,
Yates John R,
Montminy Marc
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601715
Subject(s) - creb , creb binding protein , coactivator , biology , transcription factor , phosphorylation , regulation of gene expression , transcription (linguistics) , gene expression , creb1 , gene , microbiology and biotechnology , genetics , linguistics , philosophy
A number of hormones and growth factors stimulate gene expression by promoting the phosphorylation of CREB (P‐CREB), thereby enhancing its association with the histone acetylase paralogs p300 and CBP (CBP/p300). Relative to cAMP, stress signals trigger comparable amounts of CREB phosphorylation, but have minimal effects on CRE‐dependent transcription. Here, we show that the latent cytoplasmic coactivator TORC2 mediates target gene activation in response to cAMP signaling by associating with CBP/p300 and increasing its recruitment to a subset of CREB target genes. TORC2 is not activated in response to stress signals, however; and in its absence, P‐CREB is unable to stimulate CRE‐dependent transcription, due to a block in CBP recruitment. The effect of TORC2 on CBP/p300 promoter occupancy appears pivotal because a gain of function mutant CREB polypeptide with increased affinity for CBP restored CRE‐mediated transcription in cells exposed to stress signals. Taken together, these results indicate that TORC2 is one of the long sought after cofactors that mediates the differential effects of cAMP and stress pathways on CREB target gene expression.