An order-to-disorder structural switch activates the FoxM1 transcription factor.
Elife
; 82019 05 28.
Article
en En
| MEDLINE
| ID: mdl-31134895
ABSTRACT
Intrinsically disordered transcription factor transactivation domains (TADs) function through structural plasticity, adopting ordered conformations when bound to transcriptional co-regulators. Many transcription factors contain a negative regulatory domain (NRD) that suppresses recruitment of transcriptional machinery through autoregulation of the TAD. We report the solution structure of an autoinhibited NRD-TAD complex within FoxM1, a critical activator of mitotic gene expression. We observe that while both the FoxM1 NRD and TAD are primarily intrinsically disordered domains, they associate and adopt a structured conformation. We identify how Plk1 and Cdk kinases cooperate to phosphorylate FoxM1, which releases the TAD into a disordered conformation that then associates with the TAZ2 or KIX domains of the transcriptional co-activator CBP. Our results support a mechanism of FoxM1 regulation in which the TAD undergoes switching between disordered and different ordered structures.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Activación Enzimática
/
Proteína Forkhead Box M1
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Elife
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos