Regulation of the protein stability of POSH and MLK family
Protein & Cell
; (12): 871-878, 2010.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-757431
Biblioteca responsável:
WPRO
ABSTRACT
Sequential activation of the JNK pathway components, including Rac1/Cdc42, MLKs (mixed-lineage kinases), MKK4/7 and JNKs, plays a required role in many cell death paradigms. Those components are organized by a scaffold protein, POSH (Plenty of SH3's), to ensure the effective activation of the JNK pathway and cell death upon apoptotic stimuli. We have shown recently that the expression of POSH and MLK family proteins are regulated through protein stability. By generating a variety of mutants, we provide evidence here that the Nterminal half of POSH is accountable for its stability regulation and its over-expression-induced cell death. In addition, POSH's ability to induce apoptosis is correlated with its stability as well as its MLK binding ability. MLK family's stability, like that of POSH, requires activation of JNKs. However, we were surprised to find out that the widely used dominant negative (d/n) form of c-Jun could down-regulate MLK's stability, indicating that peptide from d/n c-Jun can be potentially developed into a therapeutical drug.
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fragmentos de Peptídeos
/
Fisiologia
/
Proteínas Recombinantes
/
Proteínas Nucleares
/
Sequência de Bases
/
Transfecção
/
Transdução de Sinais
/
Linhagem Celular
/
Células PC12
/
Apoptose
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Protein & Cell
Ano de publicação:
2010
Tipo de documento:
Artigo