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Article Dans Une Revue Biochemical Journal Année : 2009

Coactivator SRC-1 is dispensable for transcriptional control by Stat3

Helena Cvijic
  • Fonction : Auteur
Kay Bauer
  • Fonction : Auteur
Dennis Löffler
  • Fonction : Auteur
Gabriele Pfeifer
  • Fonction : Auteur
Conny Blumert
  • Fonction : Auteur
Antje K. Kretzschmar
  • Fonction : Auteur
Christian Henze
  • Fonction : Auteur
Katja Brocke-Heidrich
  • Fonction : Auteur

Résumé

Steroid receptor coactivator-1 (SRC-1) has been reported to interact with and to be an essential coactivator for several members of the signal transducer and activator of transcription (STAT) family, including Stat3, the major signal transducer of interleukin-6 (IL-6). We addressed the question whether SRC-1 is crucial for IL-6- and Stat3-mediated physiological responses like myeloma cell survival and acute-phase protein induction. In fact, silencing of SRC-1 by RNA interference rapidly induced apoptosis in IL-6-dependent INA-6 human myeloma cells, comparable to what was observed upon silencing of Stat3. By chromatin immunoprecipitation at Stat3 target regions of various genes, however, we observed constitutive binding of SRC-1 that decreased when INA-6 cells were treated with IL-6. The same held true for Stat3 target genes analyzed in HepG2 hepatocellular carcinoma cells. SRC-1 knock-down studies demonstrated that Stat3-controlled promoters require neither SRC-1 nor the other p160 family members SRC-2 or SRC-3 in HepG2 cells. Furthermore, microarray expression profiling demonstrated that the responsiveness of IL-6 target genes is not affected by SRC-1 silencing. In contrast, coactivators of the CBP/p300 family proved functionally important for the transactivation potential of Stat3 and bound inducibly to Stat3 target regions. This recruitment did not depend on the presence of SRC-1. Altogether, this suggests that functional impairment of Stat3 is not involved in the induction of myeloma cell apoptosis by SRC-1 silencing. We therefore conclude that Stat3 transactivates its target genes by the recruitment of CBP/p300 coactivators and that this process generally does not require the contribution of SRC-1.

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Dates et versions

hal-00479103 , version 1 (30-04-2010)

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Helena Cvijic, Kay Bauer, Dennis Löffler, Gabriele Pfeifer, Conny Blumert, et al.. Coactivator SRC-1 is dispensable for transcriptional control by Stat3. Biochemical Journal, 2009, 420 (1), pp.123-132. ⟨10.1042/BJ20081989⟩. ⟨hal-00479103⟩

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