Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 278, Issue 32, Pages 30356-30364Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M302902200
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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.
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