Blockage of O-linked GlcNAcylation induces AMPK-dependent autophagy in bladder cancer cells.
Cell Mol Biol Lett
; 25: 17, 2020.
Article
en En
| MEDLINE
| ID: mdl-32174982
ABSTRACT
BACKGROUND:
High levels of the post-translational modification O-GlcNAcylation (O-GlcNAc) are found in multiple cancers, including bladder cancer. Autophagy, which can be induced by stress from post-translational modifications, plays a critical role in maintaining cellular homeostasis and regulating tumorigenesis. The impact of O-GlcNAcylation on autophagy in bladder cancer remains unclear. Here, we evaluate the change in autophagic activity in response to O-GlcNAcylation and explore the potential mechanisms.METHODS:
O-GlcNAcylation levels in bladder cancer cells were altered through pharmacological or genetic manipulations treating with 6-diazo-5-oxo-norleucine (DON) or thiamet-G (TG) or up- and downregulation of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA). Autophagy was determined using fluorescence microscopy and western blotting. Co-immunoprecipitation (Co-IP) assays were performed to evaluate whether the autophagy regulator AMP-activated protein kinase (AMPK) was O-GlcNAc modified.RESULTS:
Cellular autophagic flux was strikingly enhanced as a result of O-GlcNAcylation suppression, whereas it decreased at high O-GlcNAcylation levels. Phosphorylation of AMPK increased after the suppression of O-GlcNAcylation. We found that O-GlcNAcylation of AMPK suppressed the activity of this regulator, thereby inhibiting ULK1 activity and autophagy.CONCLUSION:
We characterized a new function of O-GlcNAcylation in the suppression of autophagy via regulation of AMPK. GRAPHICAL ABSTRACT Blockage of O-linked GlcNAcylation induces AMPK dependent autophagy in bladder cancer cells.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
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Neoplasias de la Vejiga Urinaria
/
Beta-N-Acetilhexosaminidasas
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Procesamiento Proteico-Postraduccional
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N-Acetilglucosaminiltransferasas
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Proteínas Quinasas Activadas por AMP
Límite:
Humans
Idioma:
En
Revista:
Cell Mol Biol Lett
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2020
Tipo del documento:
Article