Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biochim Biophys Acta Gen Subj ; 1866(12): 130238, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36044955

RESUMO

The Hippo pathway plays central roles in relaying mechanical signals during development and tumorigenesis, but how the proteostasis of the Hippo kinase MST2 is regulated remains unknown. Here, we found that chemical inhibition of proteasomal proteolysis resulted in increased levels of MST2 in human breast epithelial cells. MST2 binds SCFßTrCP E3 ubiquitin ligase and silencing ßTrCP resulted in MST2 accumulation. Site-directed mutagenesis combined with computational molecular dynamics studies revealed that ßTrCP binds MST2 via a non-canonical degradation motif. Additionally, stiffer extracellular matrix, as well as hyperactivation of integrins resulted in enhanced MST2 degradation mediated by integrin-linked kinase (ILK) and actomyosin stress fibers. Our study uncovers the underlying biochemical mechanisms controlling MST2 degradation and underscores how alterations in the microenvironment rigidity regulate the proteostasis of a central Hippo pathway component.


Assuntos
Serina-Treonina Quinase 3 , Ubiquitina-Proteína Ligases , Proteínas Contendo Repetições de beta-Transducina , Humanos , Proteínas Contendo Repetições de beta-Transducina/metabolismo , Matriz Extracelular/metabolismo , Fosforilação , Proteólise , Ubiquitina-Proteína Ligases/metabolismo , Serina-Treonina Quinase 3/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...