Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence - Sorbonne Université Access content directly
Journal Articles (Review Article) International Journal of Molecular Sciences Year : 2023

Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence

Abstract

The B-cell lymphoma 2 (Bcl-2) family of proteins is the main regulator of apoptosis. However, multiple emerging evidence has revealed that Bcl-2 family proteins are also involved in cellular senescence. On the one hand, the different expression of these proteins determines the entry into senescence. On the other hand, entry into senescence modulates the expression of these proteins, generally conferring resistance to apoptosis. With some exceptions, senescent cells are characterized by the upregulation of antiapoptotic proteins and downregulation of proapoptotic proteins. Under physiological conditions, freshly formed tetraploid cells die by apoptosis due to the tetraploidy checkpoint. However, suppression of Bcl-2 associated x protein (Bax), as well as overexpression of Bcl-2, favors the appearance and survival of tetraploid cells. Furthermore, it is noteworthy that our laboratory has shown that the joint absence of Bax and Bcl-2 antagonist/killer (Bak) favors the entry into senescence of tetraploid cells. Certain microtubule inhibitory chemotherapies, such as taxanes and vinca alkaloids, induce the generation of tetraploid cells. Moreover, the combined use of inhibitors of antiapoptotic proteins of the Bcl-2 family with microtubule inhibitors increases their efficacy. In this review, we aim to shed light on the involvement of the Bcl-2 family of proteins in the senescence program activated after tetraploidization and the possibility of using this knowledge to create a new therapeutic strategy targeting cancer cells.
Fichier principal
Vignette du fichier
2023_Barriuso_IJMS.pdf (1.81 Mo) Télécharger le fichier
Origin : Publication funded by an institution

Dates and versions

hal-04089472 , version 1 (04-05-2023)

Identifiers

Cite

Daniel Barriuso, Lucia Alvarez-Frutos, Lucia Gonzalez-Gutierrez, Omar Motiño, Guido Kroemer, et al.. Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence. International Journal of Molecular Sciences, 2023, 24 (7), pp.6374. ⟨10.3390/ijms24076374⟩. ⟨hal-04089472⟩
18 View
12 Download

Altmetric

Share

Gmail Facebook X LinkedIn More