OTUB2 Promotes Cancer Metastasis via Hippo-Independent Activation of YAP and TAZ.
Mol Cell
; 73(1): 7-21.e7, 2019 01 03.
Article
en En
| MEDLINE
| ID: mdl-30472188
ABSTRACT
The transcriptional regulators YAP and TAZ play important roles in development, physiology, and tumorigenesis and are negatively controlled by the Hippo pathway. It is yet unknown why the YAP/ TAZ proteins are frequently activated in human malignancies in which the Hippo pathway is still active. Here, by a gain-of-function cancer metastasis screen, we discovered OTUB2 as a cancer stemness and metastasis-promoting factor that deubiquitinates and activates YAP/TAZ. We found OTUB2 to be poly-SUMOylated on lysine 233, and this SUMOylation enables it to bind YAP/TAZ. We also identified a yet-unknown SUMO-interacting motif (SIM) in YAP and TAZ required for their association with SUMOylated OTUB2. Importantly, EGF and oncogenic KRAS induce OTUB2 poly-SUMOylation and thereby activate YAP/TAZ. Our results establish OTUB2 as an essential modulator of YAP/TAZ and also reveal a novel mechanism via which YAP/TAZ activity is induced by oncogenic KRAS.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Tioléster Hidrolasas
/
Células Madre Neoplásicas
/
Neoplasias de la Mama
/
Movimiento Celular
/
Péptidos y Proteínas de Señalización Intracelular
/
Proteínas Adaptadoras Transductoras de Señales
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2019
Tipo del documento:
Article
País de afiliación:
China