The cytoskeleton is a dynamic network that undergoes restructuring during various cellular events, influencing cell proliferation, differentiation, and apoptosis. Here, we report that accumulation of c-Jun, a member of the AP1 family of transcription factors that play a key role in normal and aberrant cell growth, dramatically increases upon depolymerization of the cytoskeleton, and that, unexpectedly, this increase is controlled translationally. Depolymerization of the actin or microtubule network induces an increase in c-Jun accumulation with no corresponding increase in c-Jun mRNA or in the half-life of the c-Jun protein, but rather in the translatability of its transcript. This increase is mediated by the untranslated regions (UTRs) of c-Jun mRNA, and is not dependent on activated mitogen-activated protein kinase pathways. This novel mechanism of c-Jun regulation might be relevant to physiological conditions in which c-Jun plays a pivotal role.
Bibliographical noteFunding Information:
We thank Drs M Cobb, M Karin, Y Kashman, J Kyriakis, R Prywes, R Seger, and E Shaulian for plasmids and reagents, Dr O Elroy-Stein for helpful suggestions and Dr M Yaniv for critical reading of the manuscript. This research was supported by the Israel Cancer Association and the Israel Science Foundation founded by the Israel Academy of Sciences and Humanities.
- Cell density
- Cytoskeletal network
- Translation control