Small contribution of G1 checkpoint control manipulation to modulation of p53-mediated apoptosis.

Published

Journal Article

Deregulation of the S-phase promoting E2F-1 transcription factor has been shown to cooperate with p53 to induce apoptosis. BaF3 cells undergo rapid, p53-dependent apoptosis when irradiated in the absence of IL-3. Rapid apoptosis induced by ionizing radiation (IR) coincides with attenuated p21(WAF1/Cip1) induction. Failure to adequately induce p21 could result in inappropriate release of E2F from Rb which may then cooperate with p53 to induce apoptosis in cells deprived of growth factor. We engineered BaF3 cells to express exogenous p21 and tested whether overexpressing p21 in cells irradiated in the absence of IL-3 protects from IR-induced apoptosis. Enforced p21 expression resulted in a consistent, but partial, protection of cells from undergoing IR-induced apoptosis. However, deregulating E2F activity through expression of HPV E7 failed to sensitize cells to IR-induced apoptosis in the presence of IL-3. Together, these data strongly suggest that the IL-3-responsive factors which modulate p53-mediated apoptosis in BaF3 cells are largely independent of G1 cell cycle checkpoint control mediated by p21.

Full Text

Duke Authors

Cited Authors

  • Canman, CE; Kastan, MB

Published Date

  • February 26, 1998

Published In

Volume / Issue

  • 16 / 8

Start / End Page

  • 957 - 966

PubMed ID

  • 9519869

Pubmed Central ID

  • 9519869

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/sj.onc.1201612

Language

  • eng

Conference Location

  • England