The small Rho GTPase Rac1 controls normal human dermal fibroblasts proliferation with phosphorylation of the oncoprotein c-myc
- Cell and Tissue Laboratory, URPHYM, University of Namur (FUNDP), B-5000 Namur (Belgium)
- Department of Chemistry and Biochemistry, Medical University of Sofia, 1431 Sofia (Bulgaria)
- School of Contemporary Sciences, University of Abertay, Dundee (United Kingdom)
- Laboratory of Connective Tissues Biology, CBIG/GIGA Research Center, University of Liege, B-4000 Sart Tilman (Belgium)
Proliferation of dermal fibroblasts is crucial for the maintenance of skin. The small Rho GTPase, Rac1, has been identified as a key transducer of proliferative signals in various cell types, but in normal human dermal fibroblasts its significance to cell growth control has not been studied. In this study, we applied the method of RNA interference to suppress endogenous Rac1 expression and examined the consequences on human skin fibroblasts. Rac1 knock-down resulted in inhibition of DNA synthesis. This effect was not mediated by inhibition of the central transducer of proliferative stimuli, ERK1/2 or by activation of the pro-apoptotic p38. Rather, as a consequence of the suppressed Rac1 expression we observed a significant decrease in phosphorylation of c-myc, revealing for the first time that in human fibroblasts Rac1 exerts control on proliferation through c-myc phosphorylation. Thus Rac1 activates proliferation of normal fibroblasts through stimulation of c-myc phosphorylation without affecting ERK1/2 activity.
- OSTI ID:
- 20991479
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 359, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2007.05.214; PII: S0006-291X(07)01214-4; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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