The inhibition of the expression of the small Rho GTPase Rac1 induces differentiation with no effect on cell proliferation in growing human adult keratinocytes.
[en] Rac1 is a Rho subfamily small GTPase which is highly expressed in epidermal keratinocytes. In mice the significance of Rac1 for the maintenance of the epidermis has been controversial. In keratinocytes from human origin, the role of Rac1 in the control of growth/differentiation is still obscure. In this study we used RNA interference to induce specific inhibition of Rac1 expression in cultured human keratinocytes and analyzed the consequences on proliferation and differentiation. We found that the autocrine proliferation of keratinocytes is unaltered by Rac1 silencing. However, the suppression of Rac1 induced premature differentiation as revealed by the expression of markers (keratin 10, involucrin), but the involved mechanism is independent of the activity of p38 mitogen-activated protein kinase. Rather, we found that the effects of Rac1 silencing on keratinocytes differentiation are concomitant with negative regulation of the Ser62/Thr58 phosphorylation on the transcription factor c-myc, a mechanism known to control post-translational stability of the c-myc protein. Thus, in growing human keratinocytes, Rac1 could impede the expression of premature differentiation markers, probably by exerting positive control on c-myc activity and its binding to specific promoters.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Nikolova, Ekaterina; Université de Namur ; FUNDP and University of Sofia, Bulgaria > Cell and Tissue Lab, URPHYM
Mitev, Vanio; Medical University of Sofia, Bulgaria > Dept of Chemistry and Biochemistry
Minner, Frederic; Université de Namur > Cell and Tissue Laboratory, URPHYM
Deroanne, Christophe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire 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 inhibition of the expression of the small Rho GTPase Rac1 induces differentiation with no effect on cell proliferation in growing human adult keratinocytes.
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