Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

C-myc augments gamma irradiation-induced apoptosis by suppressing bcl-x-l

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Maclean, K. H.
  • Keller, U. B.
  • Rodriguez-Galindo, C.
  • Nilsson, J. A.
  • Cleveland, John

publication date

  • October 2003

journal

  • Molecular and Cellular Biology  Journal

abstract

  • Alterations in MYC and p53 are hallmarks of cancer. p53 coordinates the response to gamma irradiation (gamma-IR) by either triggering apoptosis or cell cycle arrest. c-Myc activates the p53 apoptotic checkpoint, and thus tumors overexpressing MYC often harbor p53 mutations. Nonetheless, many of these cancers are responsive to therapy, suggesting that Myc may sensitize cells to gamma-IR independent of p53. In mouse embryo fibroblasts (MEFs) and in E micro -myc transgenic B cells in vivo, c-Myc acts in synergy with gamma-IR to trigger apoptosis, but alone, when cultured in growth medium, it does not induce a DNA damage response. Surprisingly, c-Myc also sensitizes p53-deficient MEFs to gamma-IR-induced apoptosis. In normal cells, and in precancerous B cells of E micro -myc transgenic mice, this apoptotic response is associated with the suppression of the antiapoptotic regulators Bcl-2 and Bcl-X(L) and with the concomitant induction of Puma, a proapoptotic BH3-only protein. However, in p53-null MEFs only Bcl-X(L) expression was suppressed, suggesting levels of Bcl-X(L) regulate the response to gamma-IR. Indeed, Bcl-X(L) overexpression blocked this apoptotic response, whereas bcl-X-deficient MEFs were inherently and selectively sensitive to gamma-IR-induced apoptosis. Therefore, MYC may sensitize tumor cells to DNA damage by suppressing Bcl-X.

subject areas

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Blotting, Northern
  • Cell Survival
  • Cells, Cultured
  • Comet Assay
  • DNA Damage
  • DNA, Complementary
  • Fibroblasts
  • Gamma Rays
  • Green Fluorescent Proteins
  • Immunoblotting
  • Luminescent Proteins
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Mutation
  • Neoplasms
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Tumor Suppressor Protein p53
  • bcl-X Protein
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/mcb.23.20.7256-7270.2003

PubMed ID

  • 14517295
scroll to property group menus

Additional Document Info

start page

  • 7256

end page

  • 7270

volume

  • 23

issue

  • 20

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support