The cell cycle-regulated protein human GTSE-1 controls DNA damage-induced apoptosis by affecting p53 function.
J Biol Chem
; 278(32): 30356-64, 2003 Aug 08.
Article
em En
| MEDLINE
| ID: mdl-12750368
ABSTRACT
GTSE-1 (G2 and S phase-expressed-1) protein is specifically expressed during S and G2 phases of the cell cycle. It is mainly localized to the microtubules and when overexpressed delays the G2 to M transition. Here we report that human GTSE-1 (hGTSE-1) protein can negatively regulate p53 transactivation function, protein levels, and p53-dependent apoptosis. We identified a physical interaction between the C-terminal regulatory domain of p53 and the C-terminal region of hGTSE-1 that is necessary and sufficient to down-regulate p53 activity. Furthermore, we provide evidence that hGTSE-1 is able to control p53 function in a cell cycle-dependent fashion. hGTSE-1 knock-down by small interfering RNA resulted in a S/G2-specific increase of p53 levels as well as cell sensitization to DNA damage-induced apoptosis during these phases of the cell cycle. Altogether, this work suggests a physiological role of hGTSE-1 in apoptosis control after DNA damage during S and G2 phases through regulation of p53 function.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Proteína Supressora de Tumor p53
/
Apoptose
/
Proteínas Associadas aos Microtúbulos
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article