0000000000946251

AUTHOR

Ulrich Maurer

showing 2 related works from this author

Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription

2003

AbstractRecent efforts to develop pharmacologic agents that restore function to mutant forms of p53 hold significant promise in cancer therapy. Here, we examine the effects of such pharmacologic activation of p53 function using a small molecule, PRIMA-1, and a model system employing a p53 protein fused to a mutant steroid binding domain of the murine estrogen receptor (p53ERtam) that renders it responsive only in the presence of 4-hydroxytamoxifen. In either case, p53 activation triggered apoptosis that was not inhibited by the presence of macromolecular synthesis inhibitors. This p53-induced, transcription-independent apoptosis is Bax dependent, proceeds in the absence of a nucleus, and in…

Cancer ResearchTranscription GeneticRecombinant Fusion ProteinsMutantEstrogen receptorApoptosis03 medical and health sciencesMice0302 clinical medicineBcl-2-associated X proteinProto-Oncogene ProteinsTumor Cells CulturedAnimalsHumansCloning MolecularReceptorCells Cultured030304 developmental biologybcl-2-Associated X ProteinCell NucleusProtein Synthesis Inhibitors0303 health sciencesAza CompoundsbiologyCytochrome cCytochromes cCell BiologyFibroblastsBridged Bicyclo Compounds Heterocyclic3. Good healthCell biologyTransport proteinMitochondriaProtein TransportTamoxifenProto-Oncogene Proteins c-bcl-2Receptors EstrogenOncologyApoptosis030220 oncology & carcinogenesisMutationbiology.proteinTumor Suppressor Protein p53Binding domainCancer Cell
researchProduct

p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation.

2003

The mechanism of p53-dependent apoptosis is still only partly defined. Using early-passage embryonic fibroblasts (MEF) from wild-type (wt), p53(-/-) and bax(-/-) mice, we observe a p53-dependent translocation of Bax to the mitochondria and a release of mitochondrial Cytochrome c during stress-induced apoptosis. These events proceed independent of zVAD-inhibitable caspase activation, are not prevented by dominant negative FADD (DN-FADD), but are negatively regulated by Mdm-2. Bcl-x(L) expression prevents the release of mitochondrial Cytochrome c and apoptosis, but not Bax translocation. At a single-cell level, enforced expression of p53 is sufficient to induce Bax translocation and Cytochrom…

Fas-Associated Death Domain ProteinDown-RegulationChromosomal translocationApoptosisCytochrome c GroupMitochondrionMiceBcl-2-associated X proteinFetusDownregulation and upregulationProto-Oncogene ProteinsAnimalsFADDEnzyme InhibitorsMolecular BiologyCells CulturedAdaptor Proteins Signal Transducingbcl-2-Associated X ProteinMice KnockoutbiologyOncogeneChemistryCytochrome cCell BiologyFibroblastsMolecular biologyCell biologyMitochondriaProtein TransportGene Expression RegulationProto-Oncogene Proteins c-bcl-2ApoptosisCaspasesbiology.proteinTumor Suppressor Protein p53Carrier ProteinsCell death and differentiation
researchProduct