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Molecular and Cellular Biology, March 1999, p. 1742-1750, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Cytoskeletal Network Controls c-Jun Expression and Glucocorticoid Receptor Transcriptional Activity in an Antagonistic and Cell-Type-Specific Manner

Anat Oren,1 Avia Herschkovitz,1 Iris Ben-Dror,1 Vered Holdengreber,2 Yehuda Ben-Shaul,2 Rony Seger,3 and Lily Vardimon1,*

Department of Biochemistry1 and Department of Cell Research and Immunology,2 George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, and Department of Biological Regulation, The Weizmann Institute of Science, 76100 Rehovot,3 Israel

Received 13 July 1998/Returned for modification 24 August 1998/Accepted 3 November 1998

The physical and functional link between adhesion molecules and the cytoskeletal network suggests that the cytoskeleton might mediate the transduction of cell-to-cell contact signals, which often regulate growth and differentiation in an antagonistic manner. Depolymerization of the cytoskeleton in confluent cell cultures is reportedly sufficient to initiate DNA synthesis. Here we show that depolymerization of the cytoskeleton is also sufficient to repress differentiation-specific gene expression. Glutamine synthetase is a glia-specific differentiation marker gene whose expression in the retinal tissue is regulated by glucocorticoids and is ultimately dependent on glia-neuron cell contacts. Depolymerization of the actin or microtubule network in cells of the intact retina mimics the effects of cell separation, repressing glutamine synthetase induction by a mechanism that involves induction of c-Jun and inhibition of glucocorticoid receptor transcriptional activity. Depolymerization of the cytoskeleton activates JNK and p38 mitogen-activated protein kinase and induces c-Jun expression by a signaling pathway that depends on tyrosine kinase activity. Induction of c-Jun expression is restricted to Müller glial cells, the only cells in the tissue that express glutamine synthetase and maintain the ability to proliferate upon cell separation. Our results suggest that the cytoskeletal network might play a part in the transduction of cell contact signals to the nucleus.


* Corresponding author. Mailing address: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel. Phone: 972-3-640 7019. Fax: 972-3-640 6834. E-mail: vardi{at}post.tau.ac.il.


Molecular and Cellular Biology, March 1999, p. 1742-1750, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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