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Study on the effect of IRE1α on cell growth and apoptosis via modulation PLK1 in ER stress response

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Abstract

The mammalian unfolded protein response (UPR) protects the cell against the stress of misfolded proteins in the endoplasmic reticulum (ER). Failure to adapt to ER stress causes the UPR to trigger apoptosis. Inositol-requiring enzyme-1α (IRE1α), as one of three unfolded protein sensors in UPR signaling pathways, senses ER unfolded proteins through an ER lumenal domain that becomes oligomerized during ER stress. It is known to be important for ER stress-mediated apoptosis and cell growth, but the exact molecular mechanism underlying these processes remains unexplored. In this study, we report that knockdown of IRE1α by an siRNA silencing approach enhanced, whereas its overexpression inhibited, cell proliferation in Hepatoma cells. Besides, overexpression of IRE1α induced, while its repression inhibited, ER stress-mediated apoptosis in Hepatomas cells. Furthermore, we found that overexpressed IRE1α can down-regulate Polo-like kinase 1(PLK1) from mRNA and protein two levels. IRE1α-mediated induction of apoptosis and inhibition of proliferation in response to ER stress is through downregulation PLK1, an early trigger for G2/M transition known to be participated in regulating cell proliferation and cell apoptosis. Collectively, these findings reveal a novel critical role of IRE1α in ER stress-mediated apoptosis and the molecular mechanisms involved. IRE1α may be a useful molecular target for the development of novel predictive and therapeutic strategies in cancer.

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Acknowledgments

This work was supported by the National Science Foundation of China (No. 31040019 and No. 81171697); and the Natural Science Foundation Project of CQ CSTC (No. 2011jjA10047).

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Authors and Affiliations

  1. Department of Cell Biology and Genetics, ChongQing Medical University, ChongQing, 400016, China

    Xiangzhu Li, Huifang Zhu, Wenjun Zhao, Yanna Liu, Jinghua Zhou & Feng-Jin Guo

  2. Core Facility of Development Biology, ChongQing Medical University, ChongQing, 400016, China

    Xiangzhu Li, Huifang Zhu, Huizhe Huang, Wenjun Zhao, Yanna Liu, Jinghua Zhou & Feng-Jin Guo

  3. Laboratory of Stem Cells and Tissue Engineering, ChongQing Medical University, ChongQing, 400016, China

    Rong Jiang

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  1. Xiangzhu Li
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  8. Feng-Jin Guo
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Correspondence to Feng-Jin Guo.

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Li, X., Zhu, H., Huang, H. et al. Study on the effect of IRE1α on cell growth and apoptosis via modulation PLK1 in ER stress response. Mol Cell Biochem 365, 99–108 (2012). https://doi.org/10.1007/s11010-012-1248-4

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  • DOI: https://doi.org/10.1007/s11010-012-1248-4

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