ArticleProceedings of the National Academy of Sciences of the United States of America2008
Unfolded protein response and cell death after depletion of brefeldin A-inhibited guanine nucleotide-exchange protein GBF1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed.
- Dysregulation of the MACF1-Rab14/KIF16B-FGFR Vesicular Trafficking Axis Skews MSC Lineage Commitment in Glucocorticoid-Induced Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Elucidating Pancreatic Ductal Adenocarcinoma Carcinogenesis at Single-Cell Resolution and Identifying Subtype Specific Drug Candidates.International journal of molecular sciences · 2025Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- GBF1 deficiency causes cataracts in human and mouse.Human genetics · 2024Article
- ER-associated degradation ligase HRD1 links ER stress to DNA damage repair by modulating the activity of DNA-PKcs.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Enterovirus 3A protein disrupts endoplasmic reticulum homeostasis through interaction with GBF1.Journal of virology · 2024Article
- Aneuploidy underlies brefeldin A-induced antifungal drug resistance inFrontiers in cellular and infection microbiology · 2024Article
- COPI Vesicle Disruption Inhibits Mineralization via mTORC1-Mediated Autophagy.International journal of molecular sciences · 2023Article
- Intracellular FGF1 protects cells from apoptosis through direct interaction with p53.Cellular and molecular life sciences : CMLS · 2023Article
- TMEM127 suppresses tumor development by promoting RET ubiquitination, positioning, and degradation.Cell reports · 2023Article
- Genomics of Wolfram Syndrome 1 (WFS1).Biomolecules · 2023Review
- Site-specific phosphorylations of the Arf activator GBF1 differentially regulate GBF1 function in Golgi homeostasis and secretion versus cytokinesis.Scientific reports · 2023Article
- The Unfolded Protein Response and Its Implications for Novel Therapeutic Strategies in Inflammatory Bowel Disease.Biomedicines · 2023Review
- Human skin specific long noncoding RNA HOXC13-AS regulates epidermal differentiation by interfering with Golgi-ER retrograde transport.Cell death and differentiation · 2023Article
- Protein folding stress potentiates NLRP1 and CARD8 inflammasome activation.Cell reports · 2023Article
- Quantitative Measurement of Transthyretin Mistargeting by Proximity Labeling and Parallel Reaction Monitoring.Frontiers in chemical biology · 2023Article
- Gene expression patterns associated with caudal fin shape in the cichlidHydrobiologia · 2023Article
- Viral protein engagement of GBF1 induces host cell vulnerability through synthetic lethality.The Journal of cell biology · 2022Article
- Tunicamycin Protects against LPS-Induced Lung Injury.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Cargo receptor-assisted endoplasmic reticulum export of pathogenic α1-antitrypsin polymers.Cell reports · 2021Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Guanine nucleotide-exchange factors (GEFs) activate ADP-ribosylation factor (ARF) GTPases that recruit coat proteins to membranes to initiate transport vesicle formation. Three mammalian GEFs are inhibited by brefeldin A (BFA). GBF1, predominantly associated with cis-Golgi membranes, functions early in the secretory pathway, whereas BIG1 and BIG2 act in trans-Golgi or later sites. Perturbation of endoplasmic reticulum (ER) functions can result in accumulation of unfolded or misfolded proteins that causes ER stress and unfolded protein response (UPR), with accumulation of ER stress response element (ERSE) gene products. BFA treatment of cells causes accumulation of proteins in the ER, ER stress, and ultimately apoptosis. To assess involvement of BFA-sensitive GEFs in the damage resulting from prolonged BFA treatment, HepG2 cells were selectively depleted of BIG1, BIG2, or GBF1 by using specific siRNA. Only GBF1 siRNA dramatically slowed cell growth, led to cell-cycle arrest in G(0)/G(1) phase, and caused dispersion of Golgi markers beta-COP and GM130, whereas ER structure appeared intact. GBF1 depletion also significantly increased levels of ER proteins calreticulin and protein disulfide isomerase (PDI). Proteomic analysis identified ER chaperones involved in the UPR that were significantly increased in amounts in GBF1-depleted cells. Upon ER stress, transcription factor ATF6 translocates from the ER to Golgi, where it is sequentially cleaved by site 1 and site 2 proteases, S1P and S2P, to a 50-kDa form that activates transcription of ERSE genes. Depletion of GBF1, but not BIG1 or BIG2, induced relocation of S2P from Golgi to ER with proteolysis of ATF6 followed by up-regulation of ER chaperones, mimicking a UPR response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.