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

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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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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Keywords

  • IGF-1
  • Akt, p53
  • p21
  • UV and apoptosis

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