ERK signaling regulates tumor promoter induced c-Jun recruitment at the Fra-1 promoter.
Fra-1 as an integral part of AP-1 (Jun/Fos) drives transcriptional programs involved in several physiologic and pathologic processes. It is also critical for tumor cell motility and metastasis. We have previously shown that two critical elements of Fra-1 promoter, the upstream TPA response element (TRE) and the serum response element (SRE), are necessary for its induction in response to phorbol esters in human pulmonary epithelial cell lines. Here, we have investigated the roles of various MAP kinases in regulating Fra-1 expression in response to TPA. Using pharmacologic and genetic tools, we demonstrate a prominent role for ERK1/2, but not JNK1/2 and p38, signaling in the TPA-induced activation of specific transcription factors that bind to the AP1 site and the SRE. Inhibition of ERK1/2 pathway suppresses Elk1 activation, and c-Jun and Fra-2 recruitment to the promoter.
Adiseshaiah
Pavan
P
Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Room E7610, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Li
Jinfang
J
Vaz
Michelle
M
Kalvakolanu
Dhananjaya V
DV
Reddy
Sekhar P
SP
D051921:Fos-Related Antigen-2 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D020218:Response Elements; D027602:Serum Response Element; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000099169:Fos-Related Antigen 1
D051921:Fos-Related Antigen-2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D013755:Tetradecanoylphorbol Acetate; D000099169:Fos-Related Antigen 1