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ARF triggers cell G1 arrest by a P53 independent ERK pathway

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Abstract

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.

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Abbreviations

ERK:

Extracellular signal-regulated kinase

MEK:

MARK/ERK kinase 1

MAPK:

Mitogen-activated protein kinase

MDM2:

Murine double minute 2

PI:

Propidium iodide

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People’s Republic of China

    Hansong Du

  2. Department of Biochemistry, Basic Medical College of Wuhan University, Wuhan, 430071, People’s Republic of China

    Weiqi Yao, Min Fang & Dongcheng Wu

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  1. Hansong Du
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  2. Weiqi Yao
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  3. Min Fang
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  4. Dongcheng Wu
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Correspondence to Dongcheng Wu.

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Du, H., Yao, W., Fang, M. et al. ARF triggers cell G1 arrest by a P53 independent ERK pathway. Mol Cell Biochem 357, 415–422 (2011). https://doi.org/10.1007/s11010-011-0912-4

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  • DOI: https://doi.org/10.1007/s11010-011-0912-4

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