Abstract
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.
Original language | English |
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Article number | 854 |
Journal | Molecules |
Volume | 26 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2 Feb 2021 |
Bibliographical note
Publisher Copyright:© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Funding
This research was funded by The Scientific and Technological Research Council of Turkey (TUBITAK). M.T was funded by TUBITAK, 117Z848 and TUBITAK STAR 2247 project.
Funders | Funder number |
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TUBITAK | 117Z848, STAR 2247 |
Türkiye Bilimsel ve Teknolojik Araştirma Kurumu |
Keywords
- Autophagy
- Bag-1
- Bcl-2
- Beclin 1
- Breast cancer