STAT3 Acts as a Co-activator of Glucocorticoid Receptor Signaling

Zhang, Zhixin; Jones, Simon A.; Hagood, James S.; Fuentes, Nelson; Fuller, Gerald M.

doi:10.1074/jbc.272.49.30607

Cited by 212 publications

(143 citation statements)

References 47 publications

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“…The 2.25-fold induction in wild type promoter activity by 0.1 M DEX in the presence of 50 ng/ml IL-6 compared with IL-6 treatment of pGL3-600 alone was statistically significant (p ϭ 0.0063) (Fig. 7A, white bars), consistent with a previous report (33). In contrast, when all three type II IL-6REs were deleted, 0.1 M DEX failed to potentiate the residual promoter activity in the presence of IL-6 (Fig.…”

Section: Dexamethasone Potentiates Il-6-induced Activation Of the Humsupporting

confidence: 81%

Functional Analysis of Interleukin 6 Response Elements (IL-6REs) on the Human γ-Fibrinogen Promoter

Duan

Simpson-Haidaris

2003

Journal of Biological Chemistry

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Several families of transcription factors play important roles in modulating liver-specific gene expression during an acute phase response (APR). Stat3/APR factor is the main transactivator of gene expression by the interleukin (IL)-6 family of cytokines signaling through gp130. During an APR, fibrinogen (FBG) genes are coordinately upregulated by IL-6 and glucocorticoids. Except for rat ␥FBG, attempts to demonstrate direct binding of IL-6-activated Stat3 to FBG CTGGGAA promoter elements have not been successful. Herein we show the presence of three functional type II IL-6 response elements (IL-6REs) on the human ␥FBG promoter and that the magnitude of Stat3 binding to these elements correlates negatively with their functional activity in reporter gene assays. Stat3-specific binding to ␥FBG IL-6REs was confirmed by cross-competition with ␣ 2 -macroglobulin IL-6RE and specific interactions with anti-Stat3 in electrophoretic mobility shift assays. All type II IL-6REs contributed to full promoter activity; however, transactivation from Site II at ؊306 to ؊301 was strongest. In contrast to a previous report, IL-6 failed to induce activation of serum amyloid A-activating factor-1/c-Myc-associated zinc finger protein (SAF-1/MAZ), and mutation of the SAF-1RE had little effect on IL-6 induction of ␥FBG promoter activity. In the absence of a functional glucocorticoid receptor response element, dexamethasone potentiated IL-6-induced ␥FBG promoter activity 2-fold, requiring promoter-proximal Site I and Site II; the promoter-distal Site III had no effect on dexamethasone potentiation of IL-6-induced promoter activity. Notably the propensity for Stat3 binding to human ␥FBG IL-6REs was low compared with Stat3 binding to the ␣ 2 -macroglobulin IL-6RE. Together these data suggest that Stat3 transactivation via IL-6REs on FBG promoters likely involves participation of additional transcription factors and/or coactivators to achieve optimal coordinated up-regulation during an APR.

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Section: Dexamethasone Potentiates Il-6-induced Activation Of the Humsupporting

confidence: 81%

Functional Analysis of Interleukin 6 Response Elements (IL-6REs) on the Human γ-Fibrinogen Promoter

Duan

Simpson-Haidaris

2003

Journal of Biological Chemistry

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“…Importantly, this GRmediated transcriptional control is intact in liver cells expressing only GR dim (Tronche et al, 2004). In a similar fashion, STAT3 and GR can physically interact and cooperate to activate promoters containing either STAT or GR binding sites (De Miguel et al, 2003;Kordula and Travis, 1996;Lerner et al, 2003;Takeda et al, 1998;Zhang et al, 1997).…”

Section: A Clarkmentioning

confidence: 99%

Anti-inflammatory functions of glucocorticoid-induced genes

Clark

2007

Molecular and Cellular Endocrinology

238

193

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“…In this regard, a number of proteins have been reported to interact with STAT family proteins. For instance, Sp1 has been reported to interact with Stat1 (Look et al, 1995), cJun with Stat3b (Schaefer et al, 1995), MCM5 with Stat1a (Zhang et al, 1998a), and the glucocorticoid receptor with Stat3, Stat5a, and Stat5b (Cella et al, 1998;Stocklin et al, 1996;Zhang et al, 1997). In addition, coactivators CBP/p300 have been shown to interact with Stat1, Stat2, Stat5a, Stat5b and Stat6 (Bhattacharya et al, 1996;Gingras et al, 1999;P®tzner et al, 1998;Zhang et al, 1996;Zhu et al, 1999).…”

Section: How Do Stat5 Proteins Regulate Transcription Of Target Genes?mentioning

confidence: 99%