2022
p16 Represses DNA Damage Repair via a Novel Ubiquitin-Dependent Signaling Cascade
Molkentine DP, Molkentine JM, Bridges KA, Valdecanas DR, Dhawan A, Bahri R, Hefner AJ, Kumar M, Yang L, Abdelhakiem M, Pifer PM, Sandulache V, Sheth A, Beadle BM, Thames HD, Mason KA, Pickering CR, Meyn RE, Skinner HD. p16 Represses DNA Damage Repair via a Novel Ubiquitin-Dependent Signaling Cascade. Cancer Research 2022, 82: 916-928. PMID: 34965932, PMCID: PMC9136619, DOI: 10.1158/0008-5472.can-21-2101.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellCarrier ProteinsCyclin-Dependent Kinase Inhibitor p16DNA DamageDNA, ViralHead and Neck NeoplasmsHumansPapillomaviridaePapillomavirus InfectionsSignal TransductionSquamous Cell Carcinoma of Head and NeckTumor Suppressor ProteinsUbiquitinUbiquitin-Protein LigasesUbiquitin-Specific Peptidase 7ConceptsUbiquitin-specific protease 7DNA damage repairDamage repairHPV-positive tumorsTranscription factor Sp1Human papillomavirusFactor Sp1Neck squamous cell carcinoma cellsDNA-damaging therapiesRenders cellsHomologous recombinationSignaling cascadesHPV-negative diseaseSquamous cell carcinoma cellsHPV-negative counterpartsHPV-positive diseaseSquamous cell carcinomaUSP7 inhibitorsDNA damageHPV-negative HNSCCFunctional roleDegradation pathwayHPV positivityPathwayUndiscovered pathways
2021
Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function
Kumar M, Molkentine D, Molkentine J, Bridges K, Xie T, Yang L, Hefner A, Gao M, Bahri R, Dhawan A, Frederick MJ, Seth S, Abdelhakiem M, Beadle BM, Johnson F, Wang J, Shen L, Heffernan T, Sheth A, Ferris RL, Myers JN, Pickering CR, Skinner HD. Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function. Nature Communications 2021, 12: 6340. PMID: 34732714, PMCID: PMC8566594, DOI: 10.1038/s41467-021-26570-8.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsApoptosisBiomarkers, TumorBRCA1 ProteinCell Line, TumorCREB-Binding ProteinE1A-Associated p300 ProteinGain of Function MutationHistone AcetyltransferasesHomologous RecombinationHumansMaleMice, NudeMutationNeoplasmsProtein DomainsSquamous Cell Carcinoma of Head and NeckXenograft Model Antitumor Assays
2010
DNA Damage Drives an Activin A–Dependent Induction of Cyclooxygenase-2 in Premalignant Cells and Lesions
Fordyce C, Fessenden T, Pickering C, Jung J, Singla V, Berman H, Tlsty T. DNA Damage Drives an Activin A–Dependent Induction of Cyclooxygenase-2 in Premalignant Cells and Lesions. Cancer Prevention Research 2010, 3: 190-201. PMID: 20028875, PMCID: PMC2954106, DOI: 10.1158/1940-6207.capr-09-0229.Peer-Reviewed Original ResearchMeSH KeywordsActivinsAtaxia Telangiectasia Mutated ProteinsBlotting, WesternBreast NeoplasmsCarcinoma in SituCarcinoma, Ductal, BreastCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p16Cyclooxygenase 2DNA DamageDNA-Binding ProteinsEnzyme-Linked Immunosorbent AssayFemaleGene ExpressionGene Expression ProfilingHumansImmunohistochemistryNeoplasm ProteinsOligonucleotide Array Sequence AnalysisPrecancerous ConditionsProtein Serine-Threonine KinasesRetinoblastoma ProteinReverse Transcriptase Polymerase Chain ReactionSignal TransductionTelomereTelomeric Repeat Binding Protein 2Tumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsCOX-2 expressionCyclooxygenase-2Activin AEpithelial cellsHigh COX-2 expressionPoor clinical outcomeCOX-2 inhibitionCOX-2 inhibitorsTumor-promoting phenotypeSynthesis of prostaglandinsDNA damageDependent inductionVariant human mammary epithelial cellsBreast epithelial cellsHuman mammary epithelial cellsGastrointestinal complicationsSystemic complicationsClinical outcomesDuctal carcinomaCell cycle arrestSitu lesionsChemopreventative agentMammary epithelial cellsCancer metastasisPremalignant cells