Mol Cell Biol 2004,
PMID: 15572696
Foulds, Charles E; Nelson, Mary L; Blaszczak, Adam G; Graves, Barbara J
Cell signaling affects gene expression by regulating the activity of transcription factors. Here, we report that mitogen-activated protein kinase (MAPK) phosphorylation of Ets-1 and Ets-2, at a conserved site N terminal to their Pointed (PNT) domains, resulted in enhanced transactivation by preferential recruitment of the coactivators CREB binding protein (CBP) and p300. We discovered this phosphorylation-augmented interaction in an unbiased affinity chromatography screen of HeLa nuclear extracts by using either mock-treated or ERK2-phosphorylated ETS proteins as ligands. Binding between purified proteins demonstrated a direct interaction. Both the phosphoacceptor site, which lies in an unstructured region, and the PNT domain were required for the interaction. Minimal regions that were competent for induced CBP/p300 binding in vitro also supported MAPK-enhanced transcription in vivo. CBP coexpression potentiated MEK1-stimulated Ets-2 transactivation of promoters with Ras-responsive elements. Furthermore, CBP and Ets-2 interacted in a phosphorylation-enhanced manner in vivo. This study describes a distinctive interface for a transcription factor-coactivator complex and demonstrates a functional role for inducible CBP/p300 binding. In addition, our findings decipher the mechanistic link between Ras/MAPK signaling and two specific transcription factors that are relevant to both normal development and tumorigenesis.
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Text Mining Data
Ets-1 → Ras/mitogen activated protein kinase: "
Ras/mitogen activated protein kinase signaling
activates Ets-1 and Ets-2 by CBP/p300 recruitment
"
Ets-2 → Ras/mitogen activated protein kinase: "
Ras/mitogen activated protein kinase signaling activates Ets-1 and Ets-2 by CBP/p300 recruitment
"
Ets-2 → MEK1: "
CBP coexpression potentiated MEK1 stimulated Ets-2 transactivation of promoters with Ras-responsive elements
"
Manually curated Databases
-
IRef Biogrid Interaction:
MED23
—
ETS1
(direct interaction, unspecified method)
-
IRef Biogrid Interaction:
CREBBP
—
ETS1
(direct interaction, unspecified method)
-
IRef Biogrid Interaction:
CREBBP
—
ETS1
(direct interaction, pull down)
-
IRef Biogrid Interaction:
ETS2
—
CREBBP
(direct interaction, unspecified method)
-
IRef Biogrid Interaction:
ETS2
—
CREBBP
(direct interaction, pull down)
-
IRef Biogrid Interaction:
EP300
—
ETS1
(direct interaction, unspecified method)
-
IRef Biogrid Interaction:
EP300
—
ETS2
(direct interaction, unspecified method)
-
Reactome Reaction:
ETS1
→
MAPK1
(reaction)
-
Reactome Reaction:
ETS2
→
MAPK1
(reaction)
-
Reactome Reaction:
ETS1
→
MAPK3
(reaction)
-
Reactome Reaction:
ETS2
→
MAPK3
(reaction)
In total, 9 gene pairs are associated to this article in curated databases