Autoinhibition and Polo-dependent multisite phosphorylation restrict activity of the histone H3 kinase Haspin to mitosis.
Mol Cell
; 52(5): 734-45, 2013 Dec 12.
Article
en En
| MEDLINE
| ID: mdl-24184212
ABSTRACT
The mitosis-specific phosphorylation of histone H3 at Thr3 (H3T3ph) plays an important role in chromosome segregation by recruiting Aurora B. H3T3 phosphorylation is catalyzed by Haspin, an atypical protein kinase whose kinase domain is intrinsically active without phosphorylation at the activation loop. Here, we report the molecular basis for Haspin inhibition during interphase and its reactivation in M phase. We identify a conserved basic segment that autoinhibits Haspin during interphase. This autoinhibition is neutralized when Cdk1 phosphorylates the N terminus of Haspin in order to recruit Polo-like kinase (Plk1/Plx1), which, in turn, further phosphorylates multiple sites at the Haspin N terminus. Although Plx1, and not Aurora B, is critical for H3T3 phosphorylation in Xenopus egg extracts, Plk1 and Aurora B both promote this modification in human cells. Thus, M phase-specific H3T3 phosphorylation is governed by the combinatorial action of mitotic kinases that neutralizes Haspin autoinhibition through a mechanism dependent on multisite phosphorylation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Histonas
/
Proteínas Serina-Treonina Quinasas
/
Proteínas de Ciclo Celular
/
Proteínas de Xenopus
/
Mitosis
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos