Histochemistry and Cell Biology

, Volume 138, Issue 3, pp 447–460

XBP1S protects cells from ER stress-induced apoptosis through Erk1/2 signaling pathway involving CHOP

Authors

    • Department of Cell Biology and GeneticsChongqing Medical University
    • Core Facility of Development BiologyChongqing Medical University
  • Yanna Liu
    • Department of Cell Biology and GeneticsChongqing Medical University
    • Core Facility of Development BiologyChongqing Medical University
  • Jinghua Zhou
    • Department of Cell Biology and GeneticsChongqing Medical University
    • Core Facility of Development BiologyChongqing Medical University
  • Suxin Luo
    • Department of Cardiology, The First Affiliated HospitalChongqing Medical University
  • Wenjun Zhao
    • Department of Cell Biology and GeneticsChongqing Medical University
    • Core Facility of Development BiologyChongqing Medical University
  • Xiangzhu Li
    • Department of Cell Biology and GeneticsChongqing Medical University
    • Core Facility of Development BiologyChongqing Medical University
  • Chuanju Liu
    • Department of Orthopaedic Surgery and Department of Cell BiologyNew York University School of Medicine
Original Paper

DOI: 10.1007/s00418-012-0967-7

Cite this article as:
Guo, F., Liu, Y., Zhou, J. et al. Histochem Cell Biol (2012) 138: 447. doi:10.1007/s00418-012-0967-7

Abstract

The mammalian unfolded protein response (UPR) protects the cell against the stress of misfolded proteins in the endoplasmic reticulum (ER), and the transcription factor X-box binding protein 1 spliced (XBP1S), a regulator of the UPR, is known to be important for ER stress (ERS)-mediated apoptosis and cell growth, but the molecular mechanism underlying these processes remains unexplored. Here, we report that knockdown of XBP1S by an siRNA silencing approach increased the expression of ERS-associated molecules. The overexpression of XBP1S stimulated, whereas its knockdown inhibited, cell proliferation in chondrocytes and chondrosarcoma cells; in addition, overexpression of XBP1S inhibited, while its repression enhanced, ERS-mediated apoptosis in chondrocytes and chondrosarcoma cells. Furthermore, XBP1S-mediated inhibition of apoptosis in response to ERS is through the Erk1/2 signaling pathway and down-regulation CHOP transcription factor. CHOP is one of the key downstream molecules known to be involved in ERS-mediated apoptosis. Collectively, these findings reveal a novel critical role of XBP1S in ERS-mediated apoptosis and the molecular mechanisms involved.

Keywords

Endoplasmic reticulum stressApoptosisUnfolded protein responseX-box binding protein 1 splicedCHOP

Copyright information

© Springer-Verlag 2012