Original Paper

Histochemistry and Cell Biology

, Volume 138, Issue 3, pp 447-460

First online:

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

  • Feng-Jin GuoAffiliated withDepartment of Cell Biology and Genetics, Chongqing Medical UniversityCore Facility of Development Biology, Chongqing Medical University Email author 
  • , Yanna LiuAffiliated withDepartment of Cell Biology and Genetics, Chongqing Medical UniversityCore Facility of Development Biology, Chongqing Medical University
  • , Jinghua ZhouAffiliated withDepartment of Cell Biology and Genetics, Chongqing Medical UniversityCore Facility of Development Biology, Chongqing Medical University
  • , Suxin LuoAffiliated withDepartment of Cardiology, The First Affiliated Hospital, Chongqing Medical University
  • , Wenjun ZhaoAffiliated withDepartment of Cell Biology and Genetics, Chongqing Medical UniversityCore Facility of Development Biology, Chongqing Medical University
  • , Xiangzhu LiAffiliated withDepartment of Cell Biology and Genetics, Chongqing Medical UniversityCore Facility of Development Biology, Chongqing Medical University
  • , Chuanju LiuAffiliated withDepartment of Orthopaedic Surgery and Department of Cell Biology, New York University School of Medicine

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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), 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