Organochlorine-mediated potentiation of the general coactivator p300 through p38 mitogen-activated protein kinase

Melyssa R. Bratton, Daniel E. Frigo, Katinka A. Vigh-Conrad, Daju Fan, Scott Wadsworth, John A. Mclachlan, Matthew E. Burow

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


The activity of nuclear transcription factors is often regulated by specific kinase-signaling pathways. We have previously shown that the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) stimulates activator protein-1 activity through the p38 mitogen-activated protein kinase (MAPK). Here, we show that DDT and its metabolites also stimulate the transcriptional activity of cyclic adenosine monophosphate response element-binding protein and Elk1 and potentiate gene expression through cyclic adenosine monophosphate and hypoxia response elements. Because DDT stimulates gene expression through various transcription factors and hence multiple response elements, we hypothesized that p38 signaling targets a common shared transcriptional activator. Here, we demonstrate using both pharmacological and molecular techniques, the general coactivator p300 is phosphorylated and potentiated by the p38 MAPK signaling cascade. We further show that p38 directly phosphorylates p300 in its N-terminus. These results, together with our previous work, suggest that p38 stimulates downstream transcription factors in part by targeting the general coactivator p300.

Original languageEnglish (US)
Pages (from-to)106-113
Number of pages8
Issue number1
StatePublished - 2009

ASJC Scopus subject areas

  • Cancer Research


Dive into the research topics of 'Organochlorine-mediated potentiation of the general coactivator p300 through p38 mitogen-activated protein kinase'. Together they form a unique fingerprint.

Cite this