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The diverse functions of GAPDH: Views from different subcellular compartments
Open accessAbstract
Multiple roles for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) have been recently appreciated. In addition to the cytoplasm where the majority of GAPDH is located under the basal condition, GAPDH is also found in the particulate fractions, such as the nucleus, the mitochondria, and the small vesicular fractions. When cells are exposed to various stressors, dynamic subcellular re-distribution of GAPDH occurs. Here we review these multifunctional properties of GAPDH, especially linking them to its oligomerization, posttranslational modification, and subcellular localization. This includes mechanistic descriptions of how S-nitrosylation of GAPDH under oxidative stress may lead to cell death/dysfunction via nuclear translocation of GAPDH, which is counteracted by a cytosolic GOSPEL. GAPDH is also involved in various diseases, especially neurodegenerative disorders and cancers. Therapeutic strategies to these conditions based on molecular understanding of GAPDH are discussed.
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“Redox changes may also affect posttranslational modifications of GAPDH, altering its binding to mRNA, metabolites, as well as its localization within the cell (113, 114).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [114]
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Metadata
- Authors
- Tristan, C., Shahani, N., Sedlak, T. W., & Sawa, A.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Sawa, Akira
- Venue
- Cellular Signalling
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 23
- Issue
- 2
- Pages
- 317-323
- ISSN
- 0898-6568 (ISSN-L)
- PMC
- PMC3084531
- OpenAlex
- W2139503567
- Cited by
- 663
- References
- 86
- Citations by year
- 2026: 43 · 2025: 49 · 2024: 34 · 2023: 42 · 2022: 47 · 2021: 67 · 2020: 53 · 2019: 37 · 2018: 38 · 2017: 49 · 2016: 40 · 2015: 37 · 2014: 37 · 2013: 37 · 2012: 37
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cellular Signalling (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- USPHS (MH-084018, MH-069853, MH-085226, MH-088753)
- Stanley
- CHDI
- HighQ
- RUSK
- NARSAD
- NINDS
- S-R
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- glyceraldehyde-3-phosphate dehydrogenase, nuclear translocation, S-nitrosylation, oxidative stress, post-translational modification, protein oligomerization, Gospels, neurodegenerative diseases, cancer, cell death
- MeSH terms
- Animals, Cell Nucleus, Cytoplasm, Cytoskeleton, Glyceraldehyde-3-Phosphate Dehydrogenases, Humans, Mitochondria, Vesicular Transport Proteins
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