The diverse functions of GAPDH: views from different subcellular compartments
Carlos Tristan1, Neelam Shahani, Thomas W Sedlak
1Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Cellular Signalling
|August 24, 2010
Summary
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has diverse cellular roles beyond its known cytoplasmic function. Its dynamic relocation to organelles like the nucleus under stress impacts cell function and disease, offering therapeutic targets.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Medicine
Background:
- Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is traditionally known for its glycolytic role in the cytoplasm.
- Recent findings reveal GAPDH's presence in various subcellular compartments, including the nucleus, mitochondria, and vesicles.
- Cellular stress induces dynamic redistribution of GAPDH, highlighting its multifaceted functions.
Purpose of the Study:
- To review the multifunctional properties of GAPDH.
- To link GAPDH's functions to its oligomerization, posttranslational modification, and subcellular localization.
- To discuss GAPDH's role in diseases and potential therapeutic strategies.
Main Methods:
- Review of existing literature on GAPDH's subcellular localization and functions.
- Analysis of posttranslational modifications, including S-nitrosylation, and their impact.
- Exploration of GAPDH's role in cellular stress responses and disease pathogenesis.
Main Results:
- GAPDH exhibits dynamic subcellular re-distribution in response to cellular stressors.
- S-nitrosylation of GAPDH under oxidative stress can lead to nuclear translocation and cell dysfunction.
- Cytosolic GOSPEL protein can counteract stress-induced nuclear translocation of GAPDH.
Conclusions:
- GAPDH possesses multiple roles influenced by its localization, oligomerization, and modifications.
- Dysregulation of GAPDH is implicated in neurodegenerative disorders and cancers.
- Targeting GAPDH offers potential therapeutic avenues for various diseases.
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