Skip to main content
Open Access Publications from the University of California


UCLA Previously Published Works bannerUCLA

Pharmacologically blocking p53-dependent apoptosis protects intestinal stem cells and mice from radiation.

  • Author(s): Wang, Xinwei;
  • Wei, Liang;
  • Cramer, Julie M;
  • Leibowitz, Brian J;
  • Judge, Colleen;
  • Epperly, Michael;
  • Greenberger, Joel;
  • Wang, Fengchao;
  • Li, Linheng;
  • Stelzner, Matthias G;
  • Dunn, James CY;
  • Martin, Martin G;
  • Lagasse, Eric;
  • Zhang, Lin;
  • Yu, Jian
  • et al.

Published Web Location

Exposure to high levels of ionizing radiation (IR) leads to debilitating and dose-limiting gastrointestinal (GI) toxicity. Using three-dimensional mouse crypt culture, we demonstrated that p53 target PUMA mediates radiation-induced apoptosis via a cell-intrinsic mechanism, and identified the GSK-3 inhibitor CHIR99021 as a potent radioprotector. CHIR99021 treatment improved Lgr5+ cell survival and crypt regeneration after radiation in culture and mice. CHIR99021 treatment specifically blocked apoptosis and PUMA induction and K120 acetylation of p53 mediated by acetyl-transferase Tip60, while it had no effect on p53 stabilization, phosphorylation or p21 induction. CHIR99021 also protected human intestinal cultures from radiation by PUMA but not p21 suppression. These results demonstrate that p53 posttranslational modifications play a key role in the pathological and apoptotic response of the intestinal stem cells to radiation and can be targeted pharmacologically.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View