Facilitation of DNA damage-induced apoptosis by endoplasmic reticulum protein mitsugumin23

Biochem Biophys Res Commun. 2010 Feb 5;392(2):196-200. doi: 10.1016/j.bbrc.2010.01.013. Epub 2010 Jan 12.


The endoplasmic reticulum (ER) emanates context-dependent signals, thereby mediating cellular response to a variety of stresses. However, the underlying molecular mechanisms have been enigmatic. To better understand the signaling capacity of the ER, we focused on roles played by mitsugumin23 (MG23), a protein residing predominantly in this organelle. Overexpression of MG23 in human embryonic kidney 293T cells specifically enhanced apoptosis triggered by etoposide, a DNA-damaging anti-cancer drug. Conversely, genetic deletion of MG23 reduced susceptibility of thymocytes to DNA damage-induced apoptosis, which was demonstrated by whole-body irradiation experiments. In this setting, induction of the tumor-suppressor gene p53 was attenuated in MG23-knockout thymocytes as compared with their wild-type counterparts, consistent with the elevated radioresistance. It is therefore suggested that MG23 is an essential component of ER-generated lethal signals provoked upon DNA damage, specifying cell fate under pathophysiological conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis*
  • Cell Line
  • DNA Damage*
  • Endoplasmic Reticulum / metabolism*
  • Etoposide / pharmacology
  • Gene Knockout Techniques
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Radiation Tolerance / genetics
  • Stress, Physiological*
  • Thymus Gland / drug effects
  • Thymus Gland / metabolism*
  • Thymus Gland / radiation effects
  • Tumor Suppressor Protein p53 / metabolism


  • Antineoplastic Agents
  • Membrane Proteins
  • Tumor Suppressor Protein p53
  • mitsugumin23 protein, human
  • mitsugumin23 protein, mouse
  • Etoposide