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.
Artigo
em Inglês
| 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:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fragmentos de Peptídeos
/
Fosforilação
/
Fosfosserina
/
Proteínas Quinases
/
Especificidade por Substrato
/
Fatores de Transcrição
/
Dados de Sequência Molecular
/
Genoma Humano
/
Sequência Consenso
/
Sequência de Aminoácidos
Tipo de estudo:
Estudo diagnóstico
/
Estudo prognóstico
/
Estudo de rastreamento
Limite:
Humanos
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2007
Tipo de documento:
Artigo
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