Identification of novel substrates for human checkpoint kinase Chk1 and Chk2 through genome-wide screening using a consensus Chk phosphorylation motif
Experimental & Molecular Medicine
;
: 205-212, 2007.
Artículo
en Inglés
| WPRIM
| ID: wpr-90612
ABSTRACT
Checkpoint kinase 1 (Chk1) and Chk2 are effector kinases in the cellular DNA damage response and impairment of their function is closely related to tumorigenesis. Previous studies revealed several substrate proteins of Chk1 and Chk2, but identification of additional targets is still important in order to understand their tumor suppressor functions. In this study, we screened novel substrates for Chk1 and Chk2 using substrate target motifs determined previously by an oriented peptide library approach. The potential candidates were selected by genome-wide peptide database searches and were examined by in vitro kinase assays. ST5, HDAC5, PGC-1alpha, PP2A PR130, FANCG, GATA3, cyclin G, Rad51D and MAD1alpha were newly identified as in vitro substrates for Chk1 and/or Chk2. Among these, HDAC5 and PGC-1alpha were further analyzed to substantiate the screening results. Immunoprecipitation kinase assay of full-length proteins and site-directed mutagenesis analysis of the target motifs demonstrated that HDAC5 and PGC-1alpha were specific targets for Chk1 and/or Chk2 at least in vitro.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Fragmentos de Péptidos
/
Fosforilación
/
Fosfoserina
/
Proteínas Quinasas
/
Especificidad por Sustrato
/
Factores de Transcripción
/
Datos de Secuencia Molecular
/
Genoma Humano
/
Secuencia de Consenso
/
Secuencia de Aminoácidos
Tipo de estudio:
Estudio diagnóstico
/
Estudio pronóstico
/
Estudio de tamizaje
Límite:
Humanos
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2007
Tipo del documento:
Artículo
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