GNAQ T96S mutation abrogates the ability of wild-type GNAQ to induce apoptosis by phosphorylating annexin A2 in natural killer/T cell lymphoma.
Cancer Sci
; 113(7): 2288-2296, 2022 Jul.
Article
em En
| MEDLINE
| ID: mdl-35293080
ABSTRACT
Our previous study identified annexin A2 (ANXA2) as a Gaq-interacting partner in natural killer/T cell lymphoma (NKTCL) cells transfected with the GNAQ T96S mutation vector by immunoprecipitation and mass spectrometry; however, the detailed molecular mechanisms by which GNAQ T96S might regulate ANXA2 remain to be defined in NKTCL. Herein, we found that the GNAQ T96S mutation significantly promotes the phosphorylation of ANXA2 at the Y24 site, whereas phosphorylation of ANXA2 abolishes the ability of WT GNAQ to trigger cell apoptosis. Further investigation revealed that a GNAQ T96S peptide inhibitor induced apoptosis by competing with ANXA2 binding to GNAQ T96S in NKTCL cells. In vivo animal experiments showed that a GNAQ T96S peptide inhibitor suppresses the growth of NKTCL cells carrying the GNAQ T96S mutation. Our current data suggest a role for GNAQ T96S/Src/ANXA2 in mediating the apoptosis of NKTCL cells, and the GNAQ T96S peptide could be a promising agent for therapy in NKTCL patients.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfoma de Células T
/
Anexina A2
/
Linfoma
Limite:
Animals
Idioma:
En
Revista:
Cancer Sci
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China