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Molecular and Cellular Biology, March 1999, p. 1742-1750, Vol. 19, No. 3
Department of
Biochemistry1 and Department of Cell
Research and Immunology,
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.
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
*
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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