Cytoskeletal and cell contact control of the glucocorticoid pathway.
The cytoskeleton is a dynamic network that undergoes restructuring during a variety of cellular events including cell contact formation, cell invasion and the mitotic phase of the cell cycle. Here, we review the contribution of the cytoskeletal network to the inductive activity of glucocorticoids by focusing on the hormonal control of glutamine synthetase in the chick neural retina. Depolymerization of the cytoskeleton in cells of the intact retinal tissue inhibits the hormonal induction of glutamine synthetase, but does not alter the cellular amount of the glucocorticoid-receptor protein or the ability of the receptor molecules to translocate into the nucleus. Inhibition of glutamine synthetase induction occurs via a mechanism that involves elevation of c-Jun protein accumulation and repression of glucocorticoid-receptor transcriptional activity. Unlike growth factors and other c-Jun inducing stimuli that control the transcription of the c-Jun gene, depolymerization of the cytoskeleton elevates c-Jun accumulation by upregulating the translation of the c-Jun transcript. We postulate that the cytoskeletal-dependent increase in c-Jun accumulation is involved in cell contact control of both cell proliferation and transcriptional activity of the glucocorticoid-receptor protein.
Vardimon
Lily
L
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel. vardi@post.tau.ac.il
Ben-Dror
Iris
I
Oren
Anat
A
Polak
Pazit
P