Unknown

Dataset Information

0

Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death.


ABSTRACT: Alix/AIP1 regulates cell death in a way involving interactions with the calcium-binding protein ALG-2 and with proteins of ESCRT (endosomal sorting complex required for transport). Using mass spectrometry we identified caspase-8 among proteins co-immunoprecipitating with Alix in dying neurons. We next demonstrated that Alix and ALG-2 interact with pro-caspase-8 and that Alix forms a complex with the TNFalpha receptor-1 (TNF-R1), depending on its capacity to bind ESCRT proteins. Thus, Alix and ALG-2 may allow the recruitment of pro-caspase-8 onto endosomes containing TNF-R1, a step thought to be necessary for activation of the apical caspase. In line with this, expression of Alix deleted of its ALG-2-binding site (AlixDeltaALG-2) significantly reduced TNF-R1-induced cell death, without affecting endocytosis of the receptor. In a more physiological setting, we found that programmed cell death of motoneurons, which can be inhibited by AlixDeltaALG-2, is regulated by TNF-R1. Taken together, these results highlight Alix and ALG-2 as new actors of the TNF-R1 pathway.

SUBMITTER: Mahul-Mellier AL 

PROVIDER: S-EPMC3259881 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications


Alix/AIP1 regulates cell death in a way involving interactions with the calcium-binding protein ALG-2 and with proteins of ESCRT (endosomal sorting complex required for transport). Using mass spectrometry we identified caspase-8 among proteins co-immunoprecipitating with Alix in dying neurons. We next demonstrated that Alix and ALG-2 interact with pro-caspase-8 and that Alix forms a complex with the TNFalpha receptor-1 (TNF-R1), depending on its capacity to bind ESCRT proteins. Thus, Alix and AL  ...[more]

Similar Datasets

| S-EPMC1083949 | biostudies-literature
| S-EPMC21029 | biostudies-literature
| S-EPMC1563942 | biostudies-literature
| S-EPMC5807395 | biostudies-literature
| S-EPMC133739 | biostudies-literature
| S-EPMC8783689 | biostudies-literature
| S-EPMC2795008 | biostudies-literature
| S-EPMC3320136 | biostudies-literature
| S-EPMC5529482 | biostudies-literature
| S-EPMC9170173 | biostudies-literature