title: Dimerization of pro-oncogenic protein Anterior Gradient 2 is required for the interaction with BiP/GRP78.
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.
authors.affiliation: Medical Proteomics Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 305-333, Republic of Korea.
authors.forename: Joohyun
authors.initials: J
authors.lastname: Ryu
authors.forename: Sung Goo
authors.initials: SG
authors.lastname: Park
authors.forename: Phil Young
authors.initials: PY
authors.lastname: Lee
authors.forename: Sayeon
authors.initials: S
authors.lastname: Cho
authors.forename: Do Hee
authors.initials: DH
authors.lastname: Lee
authors.forename: Gwang Hoon
authors.initials: GH
authors.lastname: Kim
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Park
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009088:Mucoproteins; D015513:Oncogene Proteins / Q000378:metabolism*; D055503:Protein Multimerization; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: C502296:AGR2 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D003545:Cysteine