ARF triggers cell G1 arrest by a P53 independent ERK pathway
- 310 Downloads
In this study, in order to investigate the p53-independent function of p14ARF, we established p14ARF-inducible clones in the p53-deficient HCT cell line using the doxycycline-inducible expression system. A strong cell growth inhibition and G1/S arrest were observed after doxycycline induction in p53-/-HCT cells, and the cells also exhibited an obvious decrease of DNA synthesis. We further examined if the MEK/ERK pathway is involved in the G1 arrest induced by p14ARF in p53-/-HCT cells. The results indicate that ERK1/2 and p21 were activated upon p14ARF induction. Totally, the functional roles of ERK and p21 for ARF in p53-independent tumor suppression were demonstrated.
KeywordsARF P53 G1 arrest ERK
Extracellular signal-regulated kinase
MARK/ERK kinase 1
Mitogen-activated protein kinase
Murine double minute 2
The authors thank Dr. Damu Tang of the McMaster University for providing the p53-/-HCT 116 cells and the dominant-negative MEK1 (MEK1K97M) plasmid. This study was funded by grants 30670813 of the Natural Science Foundation of the People’s Republic of China.
- 29.Han JA, Kim JI, Ongusaha PP, Hwang DH, Ballou LR, Mahale A et al (2002) P53-mediated induction of Cox-2 counteracts p53- or genotoxic stress-induced apoptosis. Eur Mol Biol Organ J 21:5635–5644Google Scholar