Activation synergique du promoteur POMC PAR CRH et LIF (effet des glucocorticoides)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Communication entre les voies de signalisation du lif et de la CRH dans les cellules corticotropes hypophysaires

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

ETUDE DE L'INTERACTION DU CHAPERON MOLECULAIRE HSP90 AVEC LE RECEPTEUR DES STROGENES

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Mécanismes du contrôle de la synthèse de l'ovalbumine et de la conalbumine dans l'oviducte de poulet par l'œstradiol et la progestérone. Etudes du récepteur de l'œstradiol et des effets d'un anti-œstrogène, le tamoxifen

International audienc

Dual Specificity Phosphatase 5, a Specific Negative Regulator of ERK Signaling, Is Induced by Serum Response Factor and Elk-1 Transcription Factor.

Serum stimulation of mammalian cells induces, via the MAPK pathway, the nuclear protein DUSP5 (dual-specificity phosphatase 5), which specifically interacts with and inactivates the ERK1/2 MAP kinases. However, molecular mechanisms underlying DUSP5 induction are not well known. Here, we found that the DUSP5 mRNA induction depends on a transcriptional regulation by the MAPK pathway, without any modification of the mRNA stability. Two contiguous CArG boxes that bind serum response factor (SRF) were found in a 1 Kb promoter region, as well as several E twenty-six transcription factor family binding sites (EBS). These sites potentially bind Elk-1, a transcription factor activated by ERK1/2. Using wild type or mutated DUSP5 promoter reporters, we demonstrated that SRF plays a crucial role in serum induction of DUSP5 promoter activity, the proximal CArG box being important for SRF binding in vitro and in living cells. Moreover, in vitro and in vivo binding data of Elk-1 to the same promoter region further demonstrate a role for Elk-1 in the transcriptional regulation of DUSP5. SRF and Elk-1 form a ternary complex (Elk-1-SRF-DNA) on DUSP5 promoter, consequently providing a link to an important negative feedback tightly regulating phosphorylated ERK levels

The proximal region of <i>DUSP5</i> promoter is sufficient for its serum induction.

<p>(A) Reporter vectors harboring full-length or various truncations of the promoter region of <i>DUSP5</i> (250 ng) were transfected in NIH/3T3 cells with (black boxes) or without (white boxes) stimulation by FCS 20% for nine hours (Luciferase activity was normalized to Renilla activity). Basal luciferase activities were related to that of full-length construct. Induced luciferase activities of each vector were reported to their own basal activity. * <i>P</i> < 0.05. (B) The sequence of the putative proximal promoter region of <i>DUSP5</i> gene is shown. Putative transcription factor binding sites are indicated: two contiguous CArG boxes potentially implicated in binding of SRF, two EBS sequences GGA(A/C) potentially implicated in binding of Elk-1, one putative Lef-TCF binding site (Wnt/ β-catenin pathway), and one cAMP response element (CRE).</p