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Vol. 10, Issue 11, 3787-3799, November 1999
HSP Research Institute, Kyoto Research Park, Shimogyo-ku,
Kyoto 600-8813, Japan
The unfolded protein response (UPR) controls the levels of
molecular chaperones and enzymes involved in protein folding in the
endoplasmic reticulum (ER). We recently isolated ATF6 as a candidate for mammalian UPR-specific transcription factor. We report
here that ATF6 constitutively expressed as a 90-kDa protein (p90ATF6)
is directly converted to a 50-kDa protein (p50ATF6) in ER-stressed
cells. Furthermore, we showed that the most important consequence of
this conversion was altered subcellular localization; p90ATF6 is
embedded in the ER, whereas p50ATF6 is a nuclear protein. p90ATF6 is a
type II transmembrane glycoprotein with a hydrophobic stretch in the
middle of the molecule. Thus, the N-terminal half containing a basic
leucine zipper motif is oriented facing the cytoplasm. Full-length ATF6
as well as its C-terminal deletion mutant carrying the transmembrane
domain is localized in the ER when transfected. In contrast, mutant
ATF6 representing the cytoplasmic region translocates into the nucleus
and activates transcription of the endogenous GRP78/BiP gene. We
propose that ER stress-induced proteolysis of membrane-bound p90ATF6
releases soluble p50ATF6, leading to induced transcription in the
nucleus. Unlike yeast UPR, mammalian UPR appears to use a system
similar to that reported for cholesterol homeostasis.
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M. J. Turner, D. P. Sowders, M. L. DeLay, R. Mohapatra, S. Bai, J. A. Smith, J. R. Brandewie, J. D. Taurog, and R. A. Colbert HLA-B27 Misfolding in Transgenic Rats Is Associated with Activation of the Unfolded Protein Response J. Immunol., August 15, 2005; 175(4): 2438 - 2448. [Abstract] [Full Text] [PDF]
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M. Thomas, Z. Yu, N. Dadgar, S. Varambally, J. Yu, A. M. Chinnaiyan, and A. P. Lieberman The Unfolded Protein Response Modulates Toxicity of the Expanded Glutamine Androgen Receptor J. Biol. Chem., June 3, 2005; 280(22): 21264 - 21271. [Abstract] [Full Text] [PDF]
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P. Baumeister, S. Luo, W. C. Skarnes, G. Sui, E. Seto, Y. Shi, and A. S. Lee Endoplasmic Reticulum Stress Induction of the Grp78/BiP Promoter: Activating Mechanisms Mediated by YY1 and Its Interactive Chromatin Modifiers Mol. Cell. Biol., June 1, 2005; 25(11): 4529 - 4540. [Abstract] [Full Text] [PDF]
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I. Nagamori, N. Yabuta, T. Fujii, H. Tanaka, K. Yomogida, Y. Nishimune, and H. Nojima Tisp40, a spermatid specific bZip transcription factor, functions by binding to the unfolded protein response element via the Rip pathway Genes Cells, June 1, 2005; 10(6): 575 - 594. [Abstract] [Full Text] [PDF]
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M. Abdelrahim, S. Liu, and S. Safe Induction of Endoplasmic Reticulum-induced Stress Genes in Panc-1 Pancreatic Cancer Cells Is Dependent on Sp Proteins J. Biol. Chem., April 22, 2005; 280(16): 16508 - 16513. [Abstract] [Full Text] [PDF]
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Y. Iwata and N. Koizumi An Arabidopsis transcription factor, AtbZIP60, regulates the endoplasmic reticulum stress response in a manner unique to plants PNAS, April 5, 2005; 102(14): 5280 - 5285. [Abstract] [Full Text] [PDF]
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K.-T. Chin, H.-J. Zhou, C.-M. Wong, J. M.-F. Lee, C.-P. Chan, B.-Q. Qiang, J.-G. Yuan, I. O.-l. Ng, and D.-Y. Jin The liver-enriched transcription factor CREB-H is a growth suppressor protein underexpressed in hepatocellular carcinoma Nucleic Acids Res., March 30, 2005; 33(6): 1859 - 1873. [Abstract] [Full Text] [PDF]
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J. Ramos-Castaneda, Y.-n. Park, M. Liu, K. Hauser, H. Rudolph, G. E. Shull, M. F. Jonkman, K. Mori, S. Ikeda, H. Ogawa, et al. Deficiency of ATP2C1, a Golgi Ion Pump, Induces Secretory Pathway Defects in Endoplasmic Reticulum (ER)-associated Degradation and Sensitivity to ER Stress J. Biol. Chem., March 11, 2005; 280(10): 9467 - 9473. [Abstract] [Full Text] [PDF]
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W. Vandenberghe, R. A. Nicoll, and D. S. Bredt Interaction with the Unfolded Protein Response Reveals a Role for Stargazin in Biosynthetic AMPA Receptor Transport J. Neurosci., February 2, 2005; 25(5): 1095 - 1102. [Abstract] [Full Text] [PDF]
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J. Shen, E. L. Snapp, J. Lippincott-Schwartz, and R. Prywes Stable Binding of ATF6 to BiP in the Endoplasmic Reticulum Stress Response Mol. Cell. Biol., February 1, 2005; 25(3): 921 - 932. [Abstract] [Full Text] [PDF]
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A. J. Kim, Y. Shi, R. C. Austin, and G. H. Werstuck Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3 J. Cell Sci., January 1, 2005; 118(1): 89 - 99. [Abstract] [Full Text] [PDF]
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Y. Kimata, D. Oikawa, Y. Shimizu, Y. Ishiwata-Kimata, and K. Kohno A role for BiP as an adjustor for the endoplasmic reticulum stress-sensing protein Ire1 J. Cell Biol., November 8, 2004; 167(3): 445 - 456. [Abstract] [Full Text] [PDF]
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J.-H. Hung, I.-J. Su, H.-Y. Lei, H.-C. Wang, W.-C. Lin, W.-T. Chang, W. Huang, W.-C. Chang, Y.-S. Chang, C.-C. Chen, et al. Endoplasmic Reticulum Stress Stimulates the Expression of Cyclooxygenase-2 through Activation of NF-{kappa}B and pp38 Mitogen-activated Protein Kinase J. Biol. Chem., November 5, 2004; 279(45): 46384 - 46392. [Abstract] [Full Text] [PDF]
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D. Ito, J. R. Walker, C. S. Thompson, I. Moroz, W. Lin, M. L. Veselits, A. M. Hakim, A. A. Fienberg, and G. Thinakaran Characterization of Stanniocalcin 2, a Novel Target of the Mammalian Unfolded Protein Response with Cytoprotective Properties Mol. Cell. Biol., November 1, 2004; 24(21): 9456 - 9469. [Abstract] [Full Text] [PDF]
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J. N. Lee and J. Ye Proteolytic Activation of Sterol Regulatory Element-binding Protein Induced by Cellular Stress through Depletion of Insig-1 J. Biol. Chem., October 22, 2004; 279(43): 45257 - 45265. [Abstract] [Full Text] [PDF]
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R. Sriburi, S. Jackowski, K. Mori, and J. W. Brewer XBP1: a link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum J. Cell Biol., October 11, 2004; 167(1): 35 - 41. [Abstract] [Full Text] [PDF]
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J. Shen and R. Prywes Dependence of Site-2 Protease Cleavage of ATF6 on Prior Site-1 Protease Digestion Is Determined by the Size of the Luminal Domain of ATF6 J. Biol. Chem., October 8, 2004; 279(41): 43046 - 43051. [Abstract] [Full Text] [PDF]
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K. Yamamoto, H. Yoshida, K. Kokame, R. J. Kaufman, and K. Mori Differential Contributions of ATF6 and XBP1 to the Activation of Endoplasmic Reticulum Stress-Responsive cis-Acting Elements ERSE, UPRE and ERSE-II J. Biochem., September 1, 2004; 136(3): 343 - 350. [Abstract] [Full Text] [PDF]
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D. T. Nguyen, S. Kebache, A. Fazel, H. N. Wong, S. Jenna, A. Emadali, E.-h. Lee, J. J.M. Bergeron, R. J. Kaufman, L. Larose, et al. Nck-dependent Activation of Extracellular Signal-regulated Kinase-1 and Regulation of Cell Survival during Endoplasmic Reticulum Stress Mol. Biol. Cell, September 1, 2004; 15(9): 4248 - 4260. [Abstract] [Full Text] [PDF]
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C. Chen, E. E. Dudenhausen, Y.-X. Pan, C. Zhong, and M. S. Kilberg Human CCAAT/Enhancer-binding Protein {beta} Gene Expression Is Activated by Endoplasmic Reticulum Stress through an Unfolded Protein Response Element Downstream of the Protein Coding Sequence J. Biol. Chem., July 2, 2004; 279(27): 27948 - 27956. [Abstract] [Full Text] [PDF]
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K. Zhang and R. J. Kaufman Signaling the Unfolded Protein Response from the Endoplasmic Reticulum J. Biol. Chem., June 18, 2004; 279(25): 25935 - 25938. [Full Text] [PDF]
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S. Nadanaka, H. Yoshida, F. Kano, M. Murata, and K. Mori Activation of Mammalian Unfolded Protein Response Is Compatible with the Quality Control System Operating in the Endoplasmic Reticulum Mol. Biol. Cell, June 1, 2004; 15(6): 2537 - 2548. [Abstract] [Full Text] [PDF]
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