2023
Tumor suppressor p53 regulates heat shock factor 1 protein degradation in Huntington’s disease
Mansky R, Greguske E, Yu D, Zarate N, Intihar T, Tsai W, Brown T, Thayer M, Kumar K, Gomez-Pastor R. Tumor suppressor p53 regulates heat shock factor 1 protein degradation in Huntington’s disease. Cell Reports 2023, 42: 112198. PMID: 36867535, PMCID: PMC10128052, DOI: 10.1016/j.celrep.2023.112198.Peer-Reviewed Original ResearchConceptsMajor transcription factorTumor suppressor p53Huntington's diseaseHtt aggregationTranscription factorsE3 ligase MDM2Protein degradationSuppressor p53Reciprocal regulationMutant HttP53 stabilizationMolecular differencesCell proliferationHSF1Neurodegenerative diseasesP53Most cancersNeurodegenerationP53 deletionTranscriptionDegradationDeletionAbundanceHTT
2021
Heat Shock Factor 1 Directly Regulates Postsynaptic Scaffolding PSD-95 in Aging and Huntington’s Disease and Influences Striatal Synaptic Density
Zarate N, Intihar T, Yu D, Sawyer J, Tsai W, Syed M, Carlson L, Gomez-Pastor R. Heat Shock Factor 1 Directly Regulates Postsynaptic Scaffolding PSD-95 in Aging and Huntington’s Disease and Influences Striatal Synaptic Density. International Journal Of Molecular Sciences 2021, 22: 13113. PMID: 34884918, PMCID: PMC8657899, DOI: 10.3390/ijms222313113.Peer-Reviewed Original ResearchConceptsHeat shock transcription factor 1PSD-95 levelsPSD-95 expressionPSD-95Huntington's diseaseShock transcription factor 1Synaptic protein levelsFactor 1Heat shock factor 1Direct regulatory relationshipIonotropic glutamate receptorsAge-dependent mannerShock factor 1Protein homeostasisWT miceAcute reductionSynaptic dysfunctionGene regulationTranscription factor 1Synaptic densityProtein essentialSynaptic punctaGlutamate receptorsBehavioral deficitsExcitatory synapses
2019
Mitochondrial Dysfunction in Huntington’s Disease; Interplay Between HSF1, p53 and PGC-1α Transcription Factors
Intihar TA, Martinez EA, Gomez-Pastor R. Mitochondrial Dysfunction in Huntington’s Disease; Interplay Between HSF1, p53 and PGC-1α Transcription Factors. Frontiers In Cellular Neuroscience 2019, 13: 103. PMID: 30941017, PMCID: PMC6433789, DOI: 10.3389/fncel.2019.00103.Peer-Reviewed Original ResearchMutant HttTranscription factorsMitochondrial dysfunctionPGC-1αMitochondrial functionCo-activator PGC-1αTranscription factor HSF1Main transcription factorHuntington's diseaseProtein homeostasisHSF1Medium spiny neuronsP53 levelsUnifying mechanismHuntingtin geneNeurodegenerative diseasesP53ProteinPotential roleStriatal medium spiny neuronsCAG repeatsThird mechanismMisfoldHD progressionGenes