The cell cycle-regulated protein human GTSE-1 controls DNA damage-induced apoptosis by affecting p53 function

J Biol Chem. 2003 Aug 8;278(32):30356-64. doi: 10.1074/jbc.M302902200. Epub 2003 May 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Apoptosis*
  • Blotting, Western
  • Cell Cycle
  • DNA Damage*
  • Down-Regulation
  • Flow Cytometry
  • G2 Phase
  • Gene Silencing
  • Genes, Reporter
  • Genetic Vectors
  • Humans
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / physiology*
  • Mitosis
  • Plasmids / metabolism
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Small Interfering / metabolism
  • S Phase
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Protein p53 / physiology*


  • Antibodies, Monoclonal
  • GTSE1 protein, human
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53