Identification of ADP-ribosylation factor 4 as a suppressor of N-(4-hydroxyphenyl)retinamide-induced cell death
Abstract
Yeast-based functional screening for inhibitors of Bcl-2-associated X protein (Bax)-induced cell death in yeast identified ADP-ribosylation factor 4 (ARF4) as a novel anti-apoptotic gene in human glioblastoma-derived U373MG cells. Yeast or U373MG cells that overexpressed ARF4 exhibited reduced reactive oxygen species (ROS) generation in response to Bax or N-(4-hydroxyphenyl)retinamide (4-HPR), respectively, which suggests that ROS play a role in the inhibition of cell death by ARF4. The 4-HPR-mediated phosphorylation of c-JUN N-terminal kinase, p38, and extracellular signal-regulated kinase was markedly suppressed in U373MG cells that stably expressed ARF4. Stable ARF4 transfectants were also refractory to 4-HPR-induced mitochondrial translocation of Bax, release of mitochondrial cytochrome c, and activation of caspase-3. Our results suggest that ARF4 participates in the regulation of glioblastoma apoptosis through the inhibition of stress-mediated apoptotic signals.
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The GTP-bound form of Arf4 stably associates with intracellular organelle membranes and can activate downstream effectors.
“The GTP-bound form of Arf4 stably associates with intracellular organelle membranes and can activate downstream effectors [56], [46].”
From Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development (2012) · cites this paper as [46]
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- Authors
- Woo, I. S., Eun, S. Y., Jang, H.-S., Kang, E. S., Kim, G. H., Kim, H. J., Lee, J. H., Chang, K. C., Kim, J.-H., Han, C. W., & Seo, H. G.
- Affiliations
- Gyeongsang National University (KR)
- Konkuk University (KR)
- Dongguk University (KR)
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 276
- Issue
- 1
- Pages
- 53-60
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2005061126
- Cited by
- 30
- References
- 35
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 4 · 2017: 1 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- ARF4, N-(4-hydroxyphenyl)retinamide, apoptosis, Bax, reactive oxygen species, c-Jun N-terminal kinase, p38 MAPK, ERK, cytochrome c release, Bax translocation, caspase-3, glioblastoma, U373 cells, anti-apoptotic genes, stress-induced apoptosis
- MeSH terms
- Antineoplastic Agents, Flow Cytometry, Glioblastoma, Humans, Transfection, Blotting, Western, Gene Library, Gene Expression, Mutagenesis, Site-Directed, Apoptosis, Fenretinide, Reactive Oxygen Species, Oxidative Stress, ADP-Ribosylation Factors, Two-Hybrid System Techniques, Cell Line, Tumor, JNK Mitogen-Activated Protein Kinases, Extracellular Signal-Regulated MAP Kinases, p38 Mitogen-Activated Protein Kinases, bcl-2-Associated X Protein
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