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IGF-1 activates p21 to inhibit UV-induced cell death

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Abstract

The insulin-like growth factor-1 (IGF-1) and its downstream effector Akt have been documented as survival factors in response to a variety of stress signals. In this study, we show that IGF-1 activates p21 protein expression in a p53-dependent manner. Inhibition of PI-3 kinase or ectopic expression of a dominant-negative Akt blocks the effect of IGF-1 on the upregulation of p21 expression. In addition, IGF-1 prevents the UV irradiation-mediated suppression of p21 and MDM2 expression. Furthermore, p21 is important for IGF-1-mediated cell survival upon UV irradiation. Taken together, these data indicate that IGF-1 may activate p21 in executing its survival function upon genotoxic insults.

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Acknowledgements

We thank Drs Chuxia Deng and Tyler Jacks for wild-type MEF cells and p21−/− MEF cells, Dr Cyrus Vazari for p21-adenovirus, Drs Wataru Ogawa and Takashi Matsu for Akt- and AktDN adenoviruses, and Dr Jiandong Chen for MDM2 antibodies. This work is supported by NIH Grant R01CA79804 to Z-XX and DOD Grant DAMA17-97-1-7311 to ZXX.

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  1. Ling Gu

    Present address: Harvard Skin Disease Research Center, Brigham and Woman's Hospital, Harvard Institute of Medicine, Boston, MA, 02115, USA

Authors and Affiliations

  1. Department of Biochemistry, Boston University School of Medicine, Boston, 20118, MA, USA

    Stephen A Murray, Hongwu Zheng, Ling Gu & Zhi-Xiong Jim Xiao

  2. Department of Medicine, Boston University School of Medicine, Boston, 20118, MA, USA

    Zhi-Xiong Jim Xiao

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  1. Stephen A Murray
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Correspondence to Zhi-Xiong Jim Xiao.

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Murray, S., Zheng, H., Gu, L. et al. IGF-1 activates p21 to inhibit UV-induced cell death. Oncogene 22, 1703–1711 (2003). https://doi.org/10.1038/sj.onc.1206327

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