Snapshots of a hybrid transcription factor in the Hippo pathway
Protein & Cell
;
(12): 811-819, 2010.
Artículo
en Inglés
| WPRIM
| ID: wpr-757437
ABSTRACT
The Hippo pathway plays key roles in animal development. It suppresses tumorigenesis by controlling the transcription of the target genes that are critical for cell proliferation and apoptosis. The transcriptional coactivator YAP is the major downstream effector of the Hippo signaling. Upon extracellular stimulation, a kinase cascade in the Hippo pathway phosphorylates YAP and promotes its cytoplasmic sequestration by 14-3-3 and ubiquitin-dependent degradation. When the Hippo pathway is turned off, YAP (which lacks a DNA-binding domain) is dephosphorylated and translocates to the nucleus, where it associates with the transcription factor TEAD to form a functional heterodimeric transcription factor and to promote the expression of the Hippo-responsive genes. Recently, structures of the YAP-binding domain of TEAD alone or in complex with YAP have revealed the atomic details of the TEAD-YAP interaction. Here, I review these exciting advances, propose a strategy for targeting the TEAD-YAP interaction using small molecules, and suggest potential mechanisms by which phosphorylation and 14-3-3 binding regulate the cytoplasmic retention of YAP.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Fosforilación
/
Fisiología
/
Factores de Transcripción
/
Proteínas Nucleares
/
Transducción de Señal
/
Modelos Moleculares
/
Transactivadores
/
Química
/
Proteínas Serina-Treonina Quinasas
/
Proteínas de Drosophila
Tipo de estudio:
Estudio pronóstico
Límite:
Animales
/
Humanos
Idioma:
Inglés
Revista:
Protein & Cell
Año:
2010
Tipo del documento:
Artículo
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