[Cell cycle control and self-renewal of embryonic stem cells].
On one hand, self-renewal of mouse embryonic stem (ES) cells rely exclusively upon the LIFR beta/gp130-signaling pathway and the subsequent activation of the STAT3 transcription factor. On the other hand, the much-studied cellular machinery, that is organized to collect extracellular signals, transduce them via tyrosine kinase receptors and the SOS-RAS-RAF-MEK-MAPK pathway, ultimately leading to regulation of D-type cyclin expression, while regulation of the retinoblastoma (RB) protein phosphorylation is likely not to be operative in ES cells. We hypothetize that ES cells are blinkered by the lack of RB-dependent control of the G1/S transition, and that commitment into differentiation triggers the birth of a regulatable G1 phase. We discuss how the LIFR beta/gp130-signaling pathway and the ES cell-cycle machinery may functionally interact to promote self-renewal.
Laboratoire de Biologie Moléculaire et Cellulaire, CNRS UMR 5665, INRA LA913, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon.
Pierre
P
Savatier
Marielle
M
Afanassieff
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D002453:Cell Cycle; D002454:Cell Differentiation; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology*; D016193:G1 Phase; D006706:Homeostasis; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D015534:Trans-Activators / Q000502:physiology
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494199:IL6ST protein, human; D008562:Membrane Glycoproteins; D016160:Retinoblastoma Protein; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D050822:Cytokine Receptor gp130