The cell cycle-regulated protein human GTSE-1 controls DNA damage-induced apoptosis by affecting p53 function.
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.
Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie, Area Science Park, Padriciano 99, 34012 Trieste, Italy.
Martin
M
Monte
Roberta
R
Benetti
Giacomo
G
Buscemi
Peter
P
Sandy
Giannino
G
Del Sal
Claudio
C
Schneider
D000911:Antibodies, Monoclonal; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D004249:DNA Damage; D015536:Down-Regulation; D005434:Flow Cytometry; D016195:G2 Phase; D020868:Gene Silencing; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D008938:Mitosis; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D016196:S Phase; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*
D000911:Antibodies, Monoclonal; C115080:GTSE1 protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53