Co-Chaperone Bag-1 Plays a Role in the Autophagy-Dependent Cell Survival Through Beclin 1 Interaction

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Türk, Miray
Tatlı, Özge
Alkan, Hamza Furkan
Alkurt, Gizem
Dinler Doğanay, Gizem
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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.

Bag-1 , Bcl-2 , Beclin 1 , Autophagy , Breast Cancer
Turk, M., Tatli, O., Alkan, H. F., Ozfiliz Kilbas, P., Alkurt, G., & Dinler Doganay, G. (2021). Co-chaperone bag-1 plays a role in the autophagy-dependent cell survival through Beclin 1 interaction. Molecules, 26(4), 854.