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Vincristine ablation of Sirt2 induces cell apoptosis and mitophagy via Hsp70 acetylation in MDA-MB-231 cells.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2019 Apr; Vol. 162, pp. 142-153. Date of Electronic Publication: 2018 Oct 21. - Publication Year :
- 2019
-
Abstract
- Cancer cells are continuously challenged by adverse environmental stress and adopt diverse strategies to survive. Hsp70 plays pivotal roles in invasion, migration, drug resistance, and the survival of tumor cells. Hsp70 functions as molecular chaperone to protect tumor cells from stress-induced cell death. Hsp70 acetylation alters its chaperone activity in cell death pathways, but its relevance in the process of cell death and the underlying mechanisms involved are not well understood. In this study, we demonstrated that vincristine induces mitophagy via the disruption of Hsp70 binding with Sirt2, leading to Hsp70 acetylation at K126 and elevated sequestration of Bcl2 by Hsp70 for autophagosome creation. Acetylation at K126 significantly changes the physiological function of Hsp70 compared to acetylation at other sites. It also attenuates the protein folding and renaturation function of Hsp70 by altering the binding co-chaperones. In addition, acetylation at K126 inhibits Hsp70-mediated tumor cell invasion and migration, and the binding of Hsp70 to AIF1 and Apaf1 for promoting mitochondrial-mediated apoptosis. In conclusion, this study describes the molecular mechanism of vincristine induction of cell apoptosis and mitophagy via ablation of Sirt2 induced Hsp70 acetylation at K126 in MDA-MB-231 cells.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Acetylation drug effects
Apoptosis physiology
Cell Line, Tumor
Gene Knockout Techniques
HEK293 Cells
Humans
Mitophagy physiology
Sirtuin 2 antagonists & inhibitors
Antineoplastic Agents, Phytogenic pharmacology
Apoptosis drug effects
HSP70 Heat-Shock Proteins metabolism
Mitophagy drug effects
Sirtuin 2 metabolism
Vincristine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2968
- Volume :
- 162
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 30352233
- Full Text :
- https://doi.org/10.1016/j.bcp.2018.10.021