Differential role of FL-BID and t-BID during verotoxin-1-induced apoptosis in Burkitt’s lymphoma cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Oncogene Année : 2018

Differential role of FL-BID and t-BID during verotoxin-1-induced apoptosis in Burkitt’s lymphoma cells

Résumé

The globotriaosylceramide Gb3 is a glycosphingolipid expressed on a subpopulation of germinal center B lymphocytes which has been recognized as the B cell differentiation antigen CD77. Among tumoral cell types, Gb3/CD77 is strongly expressed in Burkitt's lymphoma (BL) cells as well as other solid tumors including breast, testicular and ovarian carcinomas. One known ligand of Gb3/CD77 is Verotoxin-1 (VT-1), a Shiga toxin produced in specific E. coli strains. Previously, we have reported that in BL cells, VT-1 induces apoptosis via a caspase-dependent and mitochondria-dependent pathway. Yet, the respective roles of various apoptogenic factors remained to be deciphered. Here, this apoptotic pathway was found to require cleavage of the BID protein by caspase-8 as well as activation of two other apoptogenic proteins, BAK and BAX. Surprisingly however, t-BID, the truncated form of BID resulting from caspase-8 cleavage, played no role in the conformational changes of BAK and BAX. Rather, their activation occurred under the control of full length BID (FL-BID). Indeed, introducing a non-cleavable form of BID (BID-D59A) into BID-deficient BL cells restored BAK and BAX activation following VT-1 treatment. Still, t-BID was involved along with FL-BID in the BAK-dependent and BAXdependent cytosolic release of CYT C and SMAC/DIABLO from the mitochondrial intermembrane space: FL-BID was found to control the homo-oligomerization of both BAK and BAX, likely contributing to the initial release of CYT C and SMAC/DIABLO, while t-BID was needed for their hetero-oligomerization and ensuing release amplification. Together, our results reveal a functional cooperation between BAK and BAX during VT-1-induced apoptosis and, unexpectedly, that activation of caspase-8 and production of t-BID were not mandatory for initiation of the cell death process.
Fichier principal
Vignette du fichier
Debernardi_et_al-2018-Oncogene.pdf (1.65 Mo) Télécharger le fichier
Origine Publication financée par une institution

Dates et versions

hal-03157452 , version 1 (03-03-2021)

Identifiants

Citer

Justine Debernardi, Emilie Hollville, • Marc Lipinski, Joëlle Wiels, Aude Robert. Differential role of FL-BID and t-BID during verotoxin-1-induced apoptosis in Burkitt’s lymphoma cells. Oncogene, 2018, 37 (18), pp.2410-2421. ⟨10.1038/s41388-018-0123-5⟩. ⟨hal-03157452⟩
36 Consultations
26 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More