2014
Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A
Gupta R, Dong Y, Solomon PD, Wettersten HI, Cheng CJ, Min JN, Henson J, Dogra SK, Hwang SH, Hammock BD, Zhu LJ, Reddel RR, Saltzman WM, Weiss RH, Chang S, Green MR, Wajapeyee N. Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: e3062-e3071. PMID: 25024194, PMCID: PMC4121806, DOI: 10.1073/pnas.1411370111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCyclin-Dependent Kinase Inhibitor p21HumansMiceMice, NudeMutationNeoplasms, ExperimentalTelomeraseTumor Suppressor Protein p53ConceptsP53-mediated transcriptional activationCyclin-dependent kinase inhibitor 1AMutant p53Telomerase inhibitionTumor suppressor p53Transcriptional activationSynergistic tumor suppressionTelomere dysfunctionCheckpoint proteinsP53 upregulated modulatorTumor suppressionCDK inhibitorsSuppressor p53Inhibitor 1AP53 activityTelomeraseHuman cancersCancer cell linesApoptosis inductionPharmacological inhibitionApoptosisCell linesPharmacological restorationP21Growth inhibition
2004
Essential role of limiting telomeres in the pathogenesis of Werner syndrome
Chang S, Multani AS, Cabrera NG, Naylor ML, Laud P, Lombard D, Pathak S, Guarente L, DePinho RA. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nature Genetics 2004, 36: 877-882. PMID: 15235603, DOI: 10.1038/ng1389.Peer-Reviewed Original ResearchConceptsWerner syndromeCultured cellsComplex cellular phenotypesElevated genomic instabilityDNA damage fociPremature aging syndromesWRN deficiencyReplicative senescenceCellular phenotypesGenomic instabilityAging syndromesGenetic dataMutational inactivationPremature senescenceChromosomal instabilityTelomerase expressionHair grayingPremature agingDisease phenotypeEssential roleWRNMice nullSenescenceAutosomal recessive diseaseType II diabetes
1999
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice
Rudolph K, Chang S, Lee H, Blasco M, Gottlieb G, Greider C, DePinho R. Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice. Cell 1999, 96: 701-712. PMID: 10089885, DOI: 10.1016/s0092-8674(00)80580-2.Peer-Reviewed Original ResearchConceptsOrganismal aging processTelomerase-null miceTelomerase-deficient miceTelomere functionOrganismal levelTelomere maintenanceCellular senescenceOverall fitnessPhysiological processesStress responseHematopoietic ablationGenetic instabilityTelomere lengthNull miceCritical roleLife spanWound healingAging processSpontaneous malignanciesSenescenceOrganismsFitnessPathophysiological symptomsRoleMice