Role of p53 in regulating tissue response to radiation by mechanisms independent of apoptosis.

Published

Journal Article

Radiation exposure leads to diverse outcomes in vivo across different tissues and even within the same cell lineage. The diversity of radiation response in vivo is at least partially attributable to the status of the tumor suppressor p53, a master regulator of cellular response to stress, and activation of its transcriptional targets. In certain cells, such as hematopoietic progenitors and transit amplifying cells in the gastrointestinal epithelium, activation of p53 by radiation triggers the intrinsic pathway of apoptosis. However, in many other cells, activation of p53 by radiation does not result in apoptosis, which underscores the importance of understanding the role of p53 in regulating radiation response through alternative mechanisms. In this review, we summarize recent studies using genetically engineered mice to dissect the role of p53 in 1) cells where its activation is dissociated from the intrinsic pathway of apoptosis, such as hematopoietic stem cells and vascular endothelial cells and 2) tissues where activation of the intrinsic pathway of apoptosis does not promote the acute radiation syndrome, such as the gastrointestinal epithelium. We highlight findings showing that the apoptosis-independent response of p53 to radiation in vivo can contribute to death or survival in a cell-type dependent manner, which underscores the complexity by which p53 regulates the cellular and tissue response to radiation.

Full Text

Duke Authors

Cited Authors

  • Lee, C-L; Blum, JM; Kirsch, DG

Published Date

  • October 2013

Published In

Volume / Issue

  • 2 / 5

Start / End Page

  • 412 - 421

PubMed ID

  • 24466508

Pubmed Central ID

  • 24466508

International Standard Serial Number (ISSN)

  • 2218-676X

Language

  • eng

Conference Location

  • China