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(Received for publication, September 14, 1995; and in revised form, February 5, 1996)
Interleukin-6 (IL-6) is the major cytokine inducing
transcription of human C-reactive protein (CRP) during the acute phase
response. STAT (signal transducers and activators of transcription)
family members, recently shown to be important mediators of the effects
of many cytokines including IL-6, generally induce their effects by
binding to palindromic sequences with TT(N)
AA motifs. We
report an IL-6 responsive element in the proximal region of the human
CRP 5`-flanking region that bears a TT(N)
AA motif, which we
have termed CRP acute phase response element (CRP-APRE). In Hep3B
cells, IL-6 but not interferon-
was capable of activating CAT
constructs driven by the CRP promoter containing CRP-APRE.
Overexpressed STAT3 was able to transactivate CRP-chloramphenicol
acetyltransferase constructs through the CRP-APRE and was able to
enhance endogenous CRP mRNA accumulation in response to IL-6. STAT3 (or
an antigenically related molecule) bound to the CRP-APRE in response to
IL-6. Overexpression of STAT3 in the presence of IL-6 was capable of
inducing expression of a construct consisting of the CRP-APRE and a
minimal thymidine kinase promoter lacking a C/EBP site. Taken together,
these findings indicate that STAT3 participates in the transcriptional
activation of CRP in response to IL-6.
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Y. Zhang, J. Turkson, C. Carter-Su, T. Smithgall, A. Levitzki, A. Kraker, J. J. Krolewski, P. Medveczky, and R. Jove Activation of Stat3 in v-Src-transformed Fibroblasts Requires Cooperation of Jak1 Kinase Activity J. Biol. Chem., August 4, 2000; 275(32): 24935 - 24944. [Abstract] [Full Text] [PDF]
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J.-Y. Yoo, W. Wang, S. Desiderio, and D. Nathans Synergistic Activity of STAT3 and c-Jun at a Specific Array of DNA Elements in the alpha 2-Macroglobulin Promoter J. Biol. Chem., July 6, 2001; 276(28): 26421 - 26429. [Abstract] [Full Text] [PDF]
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J. Turkson, D. Ryan, J. S. Kim, Y. Zhang, Z. Chen, E. Haura, A. Laudano, S. Sebti, A. D. Hamilton, and R. Jove Phosphotyrosyl Peptides Block Stat3-mediated DNA Binding Activity, Gene Regulation, and Cell Transformation J. Biol. Chem., November 21, 2001; 276(48): 45443 - 45455. [Abstract] [Full Text] [PDF]
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