title: ARF is not required for apoptosis in Rb mutant mouse embryos.
abstract: The retinoblastoma (RB) tumor suppressor gene occupies central roles in cell cycle control and tumor suppression. Homozygous mutant (Rb(-/-)) embryos die at E13.5-E15.5, exhibiting extensive apoptosis and inappropriate S phase entry in the central and peripheral nervous systems, liver, and ocular lens. Mice simultaneously mutant for Rb and other genes can be generated to assess the requirement for these genes in cell cycle control and apoptosis. Using such analysis, E2f-1, E2f-3, p53, and Id2 have been identified as important regulators of cell cycle control and apoptosis in Rb(-/-) embryos. Because unrestrained E2F activity in the absence of Rb function contributes to p53-dependent apoptosis in many systems, we wished to identify genes linking deregulated E2F activity to p53 activation and subsequent apoptosis. As a transcriptional target of E2F-1, a regulator of p53, and an important mediator of apoptosis, ARF was a strong candidate for such a role, especially since it can be upregulated in the absence of Rb. From the analysis of Rb/ARF compound mutants we demonstrate that ARF is not an obligatory link between Rb inactivation and p53-dependent apoptosis.
authors.affiliation: MIT Department of Biology and Center for Cancer Research, Cambridge, MA 02139, USA.
authors.forename: Kenneth Y
authors.initials: KY
authors.lastname: Tsai
authors.forename: David
authors.initials: D
authors.lastname: MacPherson
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Rubinson
authors.forename: Denise
authors.initials: D
authors.lastname: Crowley
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004622:Embryo, Mammalian / Q000166:cytology*; D016161:Genes, Retinoblastoma; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008817:Mice, Mutant Strains; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D017931:DNA Primers; D016159:Tumor Suppressor Protein p53; D020727:ADP-Ribosylation Factors