Cell Proliferation; Cells, Cultured; Fibroblasts; Humans; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Phosphorylation; Proto-Oncogene Proteins c-myc/metabolism; RNA, Small Interfering/genetics; Skin/cytology/metabolism; p38 Mitogen-Activated Protein Kinases/metabolism; rac1 GTP-Binding Protein/genetics/metabolism
Abstract :
[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Nikolova, Ekaterina; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP and University of Sofia > Labo Cellules et Tissus
Mitev, Vanio; Med University of Sofia, Bulgaria > Dept of Chem and Biochem
Zhelev, Nikolai; School of Comtempor Sciences, Univ of Abertay-Dundee
Deroanne, Christophe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire de Biologie des tissus conjonctifs
Poumay, Yves; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP > Unité de recherche et Physiologie Moléculaire > Laboratoire Cellules et Tissus
Language :
English
Title :
The small Rho GTPase Rac1 controls normal human dermal fibroblasts proliferation with phosphorylation of the oncoprotein c-myc.
Publication date :
2007
Journal title :
Biochemical and Biophysical Research Communications
ISSN :
0006-291X
eISSN :
1090-2104
Publisher :
Academic Press, San Diego, United States - California
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