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.
|Titolo:||The cell cycle-regulated protein human GTSE-1 controls DNA damage-induced apoptosis by affecting p53 function|
|Parole Chiave:||Apoptosis ; DNA Damage ; Antibodies, Monoclonal ; Blotting, Western ; Cell Cycle ; Down-Regulation ; Flow Cytometry ; G2 Phase ; Gene Silencing ; Genes, Reporter ; Genetic Vectors ; Humans ; Microscopy, Fluorescence ; Microtubule-Associated Proteins ; Mitosis ; Plasmids ; Precipitin Tests ; Protein Binding ; Protein Structure, Tertiary ; RNA, Small Interfering ; S Phase ; Transfection ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||2003|
|Digital Object Identifier (DOI):||10.1074/jbc.M302902200|
|Appare nelle tipologie:||01 - Articolo su periodico|