ER? activity depends on interaction and target site corecruitment with phosphorylated CREB1.

ABSTRACT: The two transcription factors estrogen receptor ? (ER?) and cyclic adenosine monophosphate (cAMP)-responsive element binding protein 1 (CREB1) mediate different signals, bind different response elements, and control different transcriptional programs. And yet, results obtained with transfected reporter genes suggested that their activities may intersect. We demonstrate here that CREB1 stimulates and is necessary for ER? activity on a transfected reporter gene and several endogenous targets both in response to its cognate ligand estrogen and to ligand-independent activation by cAMP. The stimulatory activity of CREB1 requires its DNA binding and activation by phosphorylation, and affects the chromatin recruitment of ER?. CREB1 and ER? are biochemically associated and share hundreds to thousands of chromatin binding sites upon stimulation by estrogen and cAMP, respectively. These shared regulatory activities may underlie the anti-apoptotic effects of estrogen and cAMP signaling in ER?-positive breast cancer cells. Moreover, high levels of CREB1 are associated with good prognosis in ER?-positive breast cancer patients, which may be because of its ability to promote ER? functions, thereby maintaining it as a successful therapeutic target.

SUBMITTER: Berto M 

PROVIDER: S-EPMC6238530 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature