Activation of the c-fos enhancer by the Erk MAP kinase pathway through two sequence elements: the c-fos AP-1 and p62TCF sites

Abstract

The c-fos enhancer can be activated by many signaling pathways through distinct elements of the enhancer. The enhancer contains at its core the serum response element (SRE) that binds serum response factor (SRF). On the 5' side of the SRE is a site for p62 TCF which binds only when SRF is bound as well. p62 TCF is encoded by three ets-related genes, Elk-1, SAP1 and SAP2. Each of these factors contain a transcriptional activation domain that is activated by phosphorylation by MAP kinases. On the 3' side of the SRE is the`c-fos AP1 site' (FAP1) whose role has been less clear. We ®nd here that the FAP1 site contributes strongly to phorbol ester (TPA) and Erk MAP kinase activation of the c-fos enhancer and that both the p62 TCF and FAP1 sites are required for e ective activation of the enhancer. We further ®nd that the FAP1 site binds ATF1 and CREB from HeLa nuclear extracts and that the phosphorylation of these factors is induced by TPA. ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinases. These results suggest a signaling pathway in which Erk MAP kinase activates the c-fos enhancer by direct phosphorylation of p62 TCF and by activation of Rsk related kinases that phosphorylate ATF1 and CREB.

Signal Pathways in Up-regulation of Chemokines by Tyrosine Kinase MER/NYK in Prostate Cancer Cells

“…When the nuclear activities of some potential transcription factors were analyzed, c-Jun and c-Fos were found to increase on NYK activation. This is consistent with MEK/ERK activation of Elk-1, which transcriptionally activates c-Fos and increases the c-Fos/c-Jun dimer binding to the AP-1 response element (47,48). Nuclear NF-B (p65 and p50) activity did not show much increase on NYK activation, and a mutant IL-8 promoter construct that lacks NF-B binding ability still responded to NYK activation.…”

Adipose tissue, obesity and adipokines: role in cancer promotion

“…Another downstream effect of JAK2 activation is the MAPK or ERK -extracellular signal regulated kinase (ERK) pathway [31]. The ERK phosphorylation cascade results in activation of transcription factors that interact and bind to serum response elements in the promoter region of the c-fos gene required for cell division [32]. Also, following JAK2 activation is initiation of PI3K [31] and Akt phosphorylation, which stimulates glucose utilization, cell growth via mTOR, cell proliferation and differential apoptosis [33].…”

Catching transcriptional regulation by thermostatistical modeling

“…Thermostatistical models involve three levels: the single cell microscopic level, the single cell mesoscopic level and the macroscopic level on the scale of cell population, see which is an activated form of CREB, and pELK1, which is an activated form of ELK1 [17,18]. Let us assume that there are 10000 molecules of pCREB, 5000 molecules of pELK1 and 1000 RNAP molecules in the nucleus, which are available for binding at the promoter.…”