Histochemistry and Cell Biology

, Volume 138, Issue 3, pp 447–460 | Cite as

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

  • Feng-Jin Guo
  • Yanna Liu
  • Jinghua Zhou
  • Suxin Luo
  • Wenjun Zhao
  • Xiangzhu Li
  • Chuanju Liu
Original Paper

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 stress Apoptosis Unfolded protein response X-box binding protein 1 spliced CHOP 

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Feng-Jin Guo
    • 1
    • 2
  • Yanna Liu
    • 1
    • 2
  • Jinghua Zhou
    • 1
    • 2
  • Suxin Luo
    • 3
  • Wenjun Zhao
    • 1
    • 2
  • Xiangzhu Li
    • 1
    • 2
  • Chuanju Liu
    • 4
  1. 1.Department of Cell Biology and GeneticsChongqing Medical UniversityChongqingChina
  2. 2.Core Facility of Development BiologyChongqing Medical UniversityChongqingChina
  3. 3.Department of Cardiology, The First Affiliated HospitalChongqing Medical UniversityChongqingChina
  4. 4.Department of Orthopaedic Surgery and Department of Cell BiologyNew York University School of MedicineNew YorkUSA

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