Co-Chaperone Bag-1 Plays a Role in the Autophagy-Dependent Cell Survival through Beclin 1 Interaction.
Bag-1
Bcl-2
Beclin 1
autophagy
breast cancer
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
06 Feb 2021
06 Feb 2021
Historique:
received:
30
10
2020
revised:
27
01
2021
accepted:
02
02
2021
entrez:
10
2
2021
pubmed:
11
2
2021
medline:
12
5
2021
Statut:
epublish
Résumé
Expression levels of the major mammalian autophagy regulator Beclin 1 and its interaction with Bcl-2 regulate the switch between autophagic cell survival and apoptotic cell death pathways. However, some of the regulators and the precise mechanisms of these processes still remain elusive. Bag-1 (Bcl-2 associated athanogene-1), a member of BAG family proteins, is a multifunctional pro-survival molecule that possesses critical functions in vital cellular pathways. Herein, we report the role of Bag-1 on Bcl-2/Beclin 1 crosstalk through indirectly interacting with Beclin 1. Pull-down experiments suggested a molecular interaction between Bag-1 and Beclin 1 in breast cancer cell lines. On the other hand, in vitro binding assays showed that Bag-1/Beclin 1 interaction does not occur directly but occurs through a mediator molecule. Bag-1 interaction with p-Beclin 1 (T119), indicator of early autophagy, is increased during nutrient starvation suggesting involvement of Bag-1 in the autophagic regulation. Furthermore, CRISPR/Cas9-mediated Bag-1 knock-out in MCF-7 cells hampered cell survival and proliferation and resulted in decreased levels of total LC3 under starvation. Collectively, we suggest that Bag-1 modulates cell survival/death decision through maintaining macroautophagy as a component of Beclin 1-associated complexes.
Identifiants
pubmed: 33561998
pii: molecules26040854
doi: 10.3390/molecules26040854
pmc: PMC7914623
pii:
doi:
Substances chimiques
BCL2-associated athanogene 1 protein
0
Beclin-1
0
DNA-Binding Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : The Scientific and Technological Research Council of Turkey
ID : 117Z848
Organisme : The Scientific and Technological Research Council of Turkey
ID : 2247
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