Rictor, an essential component of mTOR complex 2, undergoes caspase-mediated cleavage during apoptosis induced by multiple stimuli.
Apoptosis
; 26(5-6): 338-347, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33905036
ABSTRACT
Caspase-mediated cleavage of proteins ensures the irreversible commitment of cells to undergo apoptosis, and is thus a hallmark of apoptosis. Rapamycin-insensitive companion of mTOR (rictor) functions primarily as a core and essential component of mTOR complex 2 (mTORC2) to critically regulate cellular homeostasis. However, its role in the regulation of apoptosis is largely unknown. In the current study, we found that rictor was cleaved to generate two small fragments at ~ 50 kD and ~ 130 kD in cells undergoing apoptosis upon treatment with different stimuli such as the death ligand, TRAIL, and the small molecule, AZD9291. This cleavage was abolished when caspases were inhibited and could be reproduced when directly incubating rictor protein and caspase-3 in vitro. Furthermore, the cleavage site of caspase-3 on rictor was mapped at D1244 (VGVD). These findings together robustly demonstrate that rictor is a substrate of caspase-3 and undergoes cleavage during apoptosis. These results add new information for understanding the biology of rictor in the regulation of cell survival and growth.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Caspases
/
Proteína Companheira de mTOR Insensível à Rapamicina
Limite:
Humans
Idioma:
En
Revista:
Apoptosis
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos