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

Joohyun Ryu, Sung Goo Park, Phil Young Lee, Sayeon Cho, Do Hee Lee, Gwang Hoon Kim, Jeong Hoon Kim, Byoung Chul Park

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)610-615
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume430
Issue number2
DOIs
StatePublished - Jan 11 2013
Externally publishedYes

Bibliographical note

Funding Information:
We thank K.H. Bae for critical reading of manuscript. This work was supported by KRIBB and research grants from the National Research Foundation of Korea (NRF) ( PSC0011112 and 2011-0008842 ) and National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea ( A111218-CP03 ).

Keywords

  • AGR2
  • Dimerization
  • ER stress
  • UPR signaling pathway

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