Co-chaperone bag-1 plays a role in the autophagy-dependent cell survival through beclin 1 interaction

Miray Turk, Ozge Tatli, Hamza Furkan Alkan, Pelin Ozfiliz Kilbas, Gizem Alkurt, Gizem Dinler Doganay*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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 languageEnglish
Article number854
JournalMolecules
Volume26
Issue number4
DOIs
Publication statusPublished - 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.

FundersFunder number
TUBITAK117Z848, STAR 2247
Türkiye Bilimsel ve Teknolojik Araştirma Kurumu

    Keywords

    • Autophagy
    • Bag-1
    • Bcl-2
    • Beclin 1
    • Breast cancer

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