Regulation of Autophagy by Nuclear GAPDH and Its Aggregates in Cancer and Neurodegenerative Disorders.
GAPDH
aggregates
autophagy
cancer
cell death
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
26 Apr 2019
26 Apr 2019
Historique:
received:
28
03
2019
revised:
21
04
2019
accepted:
23
04
2019
entrez:
28
4
2019
pubmed:
28
4
2019
medline:
20
8
2019
Statut:
epublish
Résumé
Several studies indicate that the cytosolic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has pleiotropic functions independent of its canonical role in glycolysis. The GAPDH functional diversity is mainly due to post-translational modifications in different amino acid residues or due to protein-protein interactions altering its localization from cytosol to nucleus, mitochondria or extracellular microenvironment. Non-glycolytic functions of GAPDH include the regulation of cell death, autophagy, DNA repair and RNA export, and they are observed in physiological and pathological conditions as cancer and neurodegenerative disorders. In disease, the knowledge of the mechanisms regarding GAPDH-mediated cell death is becoming fundamental for the identification of novel therapies. Here, we elucidate the correlation between autophagy and GAPDH in cancer, describing the molecular mechanisms involved and its impact in cancer development. Since autophagy is a degradative pathway associated with the regulation of cell death, we discuss recent evidence supporting GAPDH as a therapeutic target for autophagy regulation in cancer therapy. Furthermore, we summarize the molecular mechanisms and the cellular effects of GAPDH aggregates, which are correlated with mitochondrial malfunctions and can be considered a potential therapeutic target for various diseases, including cancer and neurodegenerative disorders.
Identifiants
pubmed: 31027346
pii: ijms20092062
doi: 10.3390/ijms20092062
pmc: PMC6539768
pii:
doi:
Substances chimiques
Glyceraldehyde-3-Phosphate Dehydrogenases
EC 1.2.1.-
Types de publication
Journal Article
Review
Langues
eng
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