RT info:eu-repo/semantics/article
T1 Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence
A1 Barriuso, Daniel
A1 Alvarez-Frutos, Lucia
A1 Gonzalez-Gutierrez, Lucia
A1 Motiño, Omar
A1 Kroemer, Guido
A1 Palacios-Ramirez, Roberto
A1 Senovilla, Laura
K1 Bcl-2 family proteins
K1 apoptosis
K1 cancer
K1 senescence
K1 tetraploidy
AB 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.
PB MDPI
SN 1422-0067
YR 2023
FD 2023-03-28
LK https://uvadoc.uva.es/handle/10324/66272
UL https://uvadoc.uva.es/handle/10324/66272
LA spa
NO Int J Mol Sci. 2023 Mar 28
NO Producción Científica
DS UVaDOC
RD 28-nov-2024