JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis.
Cell Death Dis
; 1: e29, 2010.
Article
em En
| MEDLINE
| ID: mdl-21364637
ABSTRACT
Yes-associated protein (YAP) regulates DNA damage and chemosensitivity, as well as functioning as a pro-growth, cell size regulator. For both of its roles, regulation by phosphorylation is crucial. We undertook an in vitro screen to identify novel YAP kinases to discover new signaling pathways to better understand YAP's function. We identified JNK1 and JNK2 as robust YAP kinases, as well as mapped multiple sites of phosphorylation. Using inhibitors and siRNA, we showed that JNK specifically phosphorylates endogenous YAP in a number of cell types. We show that YAP protects keratinocytes from UV irradiation but promotes UV-induced apoptosis in a squamous cell carcinoma. We defined the mechanism for this dual role to be YAP's ability to bind and stabilize the pro-proliferative ΔNp63α isoform in a JNK-dependent manner. Our report indicates that an evaluation of the expression of the different isoforms of p63 and p73 is crucial in determining YAP's function.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Apoptose
/
Proteína Quinase 8 Ativada por Mitógeno
/
Proteína Quinase 9 Ativada por Mitógeno
/
Proteínas Adaptadoras de Transdução de Sinal
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido