ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals.

By Jingshi Shen, X. Chen, L. Hendershot, R. Prywes. Developmental Cell, 2002

1,486 citations recorded by the source corpus.

ATF6 is an endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ER molecular chaperones. Upon ER stress, ATF6 translocates from the ER to the Golgi where it is processed to its active form. We have found that the ER chaperone BiP/GRP78 binds ATF6 and dissociates in response to ER stress. Loss of BiP binding correlates with the translocation of ATF6 to the Golgi, which was slowed in cells overexpressing BiP. Two Golgi localization signals (GLSs) were identified in ATF6. Removal of BiP binding sites from ATF6, while retaining a GLS, resulted in its constitutive translocation to the Golgi. These results suggest that BiP retains ATF6 in the ER by inhibiting its GLSs and that dissociation of BiP during ER stress allows ATF6 to be transported to the Golgi.

Subfields: Cell Biology, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b3a50b21bb6799106f39c131f091b868d90d9cb8

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In Cell Biology

1. R. Kaufman
2. C. Hetz
3. G. Hotamışlıgil
4. D. Ron
5. F. Papa
6. Laurie H. Glimcher
7. J. Cubillos-Ruiz
8. Peter Walter

In Epidemiology

1. R. Kaufman
2. C. Hetz
3. G. Hotamışlıgil
4. F. Papa
5. Laurie H. Glimcher
6. D. Ron
7. J. Cubillos-Ruiz
8. Peter Walter

In Molecular Biology

1. R. Kaufman
2. G. Hotamışlıgil
3. C. Hetz
4. D. Ron
5. F. Papa
6. Laurie H. Glimcher
7. Peter Walter
8. Ann-Hwee Lee

Citations in the corpus

• Endoplasmic reticulum stress signaling in disease. (2006, background): “The importance of ER stress in this lipogenic signaling was demonstrated by BiP overexpression, which ameliorated SREBP induction in response to homocysteine.”
• Quality control in the endoplasmic reticulum protein factory (2003, background): “The unfolded proteins titrate BiP, releasing ATF6 for transport and subsequent cleavage by Golgi protease”
• Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer (2017, positive): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript ATF6α After BiP dissociation, ATF6α translocates to the Golgi apparatus, where it is cleaved intramembranously by site 1 and site 2 proteases to liberate an active, soluble ATF6α transcription factor (Shen et al., 2002).”
• Glaucoma (2018, positive): “The most contributions to the recorded electrode signal originate within a hemisphere with a radius of five times the electrode radius [11].”
• ER stress: Autophagy induction, inhibition and selection (2015, background): “However, the cytoplasmic domain of ATF6 is not necessary for its translocation to the Golgi apparatus (Table 1).(17)”
• The Unfolded Protein Response and Cell Fate Control. (2017, positive): “ATF6 also interacts with BiP at the ER, masking a binding site to coat protein-II (COP-II) vesicles (Shen et al., 2002).”
• Endoplasmic reticulum stress sensing in the unfolded protein response. (2013, background): “During ER stress, BiP dissociates from the lumenal domain of ATF6 (Shen et al. 2002, 2005).”