Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence.
Bcl-2 family proteins
apoptosis
cancer
senescence
tetraploidy
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
28 Mar 2023
28 Mar 2023
Historique:
received:
03
03
2023
revised:
21
03
2023
accepted:
24
03
2023
medline:
14
4
2023
entrez:
13
4
2023
pubmed:
14
4
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37047342
pii: ijms24076374
doi: 10.3390/ijms24076374
pmc: PMC10094710
pii:
doi:
Substances chimiques
Proto-Oncogene Proteins c-bcl-2
0
bcl-2-Associated X Protein
0
bcl-2 Homologous Antagonist-Killer Protein
0
Apoptosis Regulatory Proteins
0
bcl-X Protein
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Spanish Agencia Estatal de Investigacion (AEI)
ID : PID2021-126426OB-I00
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