GTSE-1 (G(2) and S phase-expressed-1) protein is specifically expressed during S and G(2) phases of the cell cycle. It is mainly localized to the microtubules and when overexpressed delays the G(2) 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/G(2)-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 G(2) phases through regulation of p53 function.
The cell cycle-regulated protein human GTSE-1 controls DNA damage-induced apoptosis by affecting p53 function / M. Monte, R. Benetti, G. Buscemi, P. Sandy, G. Del Sal, C. Schneider. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 278:32(2003), pp. 30356-30364.
The cell cycle-regulated protein human GTSE-1 controls DNA damage-induced apoptosis by affecting p53 function
G. Buscemi;
2003
Abstract
GTSE-1 (G(2) and S phase-expressed-1) protein is specifically expressed during S and G(2) phases of the cell cycle. It is mainly localized to the microtubules and when overexpressed delays the G(2) 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/G(2)-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 G(2) phases through regulation of p53 function.Pubblicazioni consigliate
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