Dimerization of pro-oncogenic protein Anterior Gradient 2 is required for the interaction with BiP/GRP78

• Published in: Biochemical and biophysical research communications 2013-01, Vol.430 (2), p.610-615
• Main Authors: Ryu, Joohyun, Park, Sung Goo, Lee, Phil Young, Cho, Sayeon, Lee, Do Hee, Kim, Gwang Hoon, Kim, Jeong-Hoon, Park, Byoung Chul
• Format: Article
• Language: English
• Subjects: AGR2; Apoptosis; Cell Line, Tumor; Cysteine - chemistry; Cysteine - metabolism; Dimerization; Endoplasmic Reticulum Stress; ER stress; Heat-Shock Proteins - chemistry; Heat-Shock Proteins - metabolism; Humans; Oncogene Proteins - metabolism; Protein Multimerization; Proteins - chemistry; Proteins - metabolism; Signal Transduction; Unfolded Protein Response; UPR signaling pathway
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.11.105

► AGR2 forms a homo-dimer through an intermolecular disulfide bond. ► Dimerization of AGR2 attenuates ER stress-induced cell death. ► Dimerization of AGR2 is required for the interaction with BiP/GRP78. Anterior Gradient 2 (AGR2), an ER stress-inducible protein, has been reported to be localized in endoplasmic reticulum (ER) and its level is elevated in numerous metastatic cancers. Recently, it has been demonstrated that AGR2 is involved in the control of ER homeostasis. However, the molecular mechanism how AGR2 regulates ER stress response remains unclear. Herein we show that AGR2 homo-dimerizes through an intermolecular disulfide bond. Moreover, dimerization of AGR2 attenuates ER stress-induced cell death through the association with BiP/GRP78. Thus, these results suggest that dimerization of AGR2 is crucial in mediating the ER stress signaling pathway.