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Molecular and Cellular Biology, October 1999, p. 7138-7146, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Interacting Regions in Stat3 and c-Jun That Participate in Cooperative Transcriptional Activation

Xiaokui Zhang, Melissa H. Wrzeszczynska, Curt M. Horvath,dagger and James E. Darnell Jr.*

Laboratory of Molecular Cell Biology, The Rockefeller University, New York, New York 10021

Received 22 March 1999/Returned for modification 21 April 1999/Accepted 9 July 1999

Independent but closely spaced DNA binding sites for Stat3 and c-Jun are required for maximal enhancer function in a number of genes, including the gene encoding the interleukin-6 (IL-6)-induced acute-phase response protein, alpha 2-macroglobulin. In addition, a physical interaction of Stat3 with c-Jun, based on yeast two-hybrid interaction experiments, has been reported. Here we confirm the existence of an interaction between Stat3 and c-Jun both in vitro, with recombinant proteins, and in vivo, during transient transfection. Using fragments of both proteins, we mapped the interactive sites to the C-terminal region of c-Jun and to two regions in Stat3, within the coiled-coil domain and in a portion of the DNA binding domain distant from DNA contact sites. In transient-transfection experiments with the alpha 2-macroglobulin enhancer, Stat3 and c-Jun cooperated to yield maximal enhancer function. Point mutations of Stat3 within the interacting domains blocked both physical interaction of Stat3 with c-Jun and their cooperation in IL-6-induced transcription directed by the alpha 2-macroglobulin enhancer. While the amino acid sequences and the three-dimensional structures of Stat3 and Stat1 cores are very similar, fragments of Stat1 failed to bind c-Jun in vitro. Although Stat1 binds in vitro to the gamma interferon gene response (GAS) element in the alpha 2-macroglobulin enhancer, Stat1 did not stimulate transcription, nor did Stat1 and c-Jun cooperate in driving transcription controlled by the alpha 2-macroglobulin enhancer.

* Corresponding author. Mailing address: Laboratory of Molecular Cell Biology, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: (212) 327-8791. Fax: (212) 327-8801. E-mail: darnell{at}rockvax.rockefeller.edu.

dagger Present address: Immunobiology Center, Mount Sinai Medical Center, New York, NY 10029.

Molecular and Cellular Biology, October 1999, p. 7138-7146, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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