Mechanisms of reversible DUB oxidation in genome stability pathways - Revision
Mechanisms of reversible DUB oxidation in genome stability pathways - Revision
批准号:
10174167
负责人:
Tony Tung Huang
金额:
$35.43万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-09-16 至 2022-08-31
关键词:
2019-nCoVAddressAdult Respiratory Distress SyndromeAffectAntiviral AgentsArrhythmiaBiochemicalBiochemistryCOVID-19COVID-19 pandemicCarcinogensCaspaseCell Cycle RegulationCell physiologyCellsCellular biologyCessation of lifeChemicalsCivilizationCleaved cellCommon Cold VirusCoronavirusCountryCouplingCysteineDNA RepairDataDeath RateDefense MechanismsDeubiquitinating EnzymeDevelopmentDiseaseDrosophila pros proteinEnvironmentEnvironmental ExposureEnvironmental PollutionEnvironmental Risk FactorEnzymesEpithelial CellsEquilibriumEventFamilyFatality rateFree RadicalsFutureGene ExpressionGenerationsGenome StabilityGoalsGrantHeavy MetalsHumanISG15 geneImmune responseIn VitroIndividualInfectionInhalationKnowledgeLeadLifeLungLung diseasesMass Spectrum AnalysisMediatingMiddle East Respiratory SyndromeMiddle East Respiratory Syndrome CoronavirusModelingModernizationMolecularNamesOxidantsOxidation-ReductionOxidative StressOxygenPathogenesisPathogenicityPathway interactionsPeptide HydrolasesPesticidesPhosphotransferasesPoisonPopulationPredispositionPrevalenceProteinsProteomeProteomicsPublishingRNAReactive Oxygen SpeciesRecombinant ProteinsRecombinantsRegulationResearchResearch ProposalsRespiratory physiologyRoleSARS coronavirusSeriesSevere Acute Respiratory SyndromeSeveritiesSourceTechniquesTestingTherapeuticUbiquitinUbiquitin Like ProteinsUbiquitinationViralVirus Diseasesbasebody systemcellular targetingcigarette smokecomorbidityenvironmental agentenzyme activityhuman coronavirusin vitro activityinfection rateinterestlysosomal proteinsmicrobialmutantnovelnovel coronavirusnovel therapeuticsnovel virusoxidationpandemic diseasepollutantpreferenceprotein degradationresponsesmall moleculesuccesstargeted treatmenttoxic metal
中文摘要
项目总结/文摘
英文摘要
PROJECT SUMMARY/ABSTRACT
The current pandemic of COVID-19 (Coronavirus Disease-2019), a respiratory disease that has
led to over 5 million confirmed cases and over 350,000 fatalities in over 100 countries since its
emergence in late 2019, is caused by a novel virus strain, SARS-CoV-2, an enveloped, positive-
sense, single-stranded RNA beta-coronavirus of the family Coronaviridae. My lab has a long-
standing interest in understanding how cellular DUBs are regulated by environmentally-produced
small molecules, including ROS, toxic heavy metals, chemical pollutants and carcinogens. Similar
to human DUBs, viral DUBs, such as the coronavirus Plpro, are proteases that cleave ubiquitin
or ubiquitin-like proteins from pro-proteins or from conjugates on target proteins. In doing so, viral
DUBs hijack the balance of ubiquitination dynamics in infected cells, potentially disrupting
numerous cellular functions, including cell cycle regulation, proteasomal and lysosomal protein
degradation, gene expression, kinase activation, DNA repair and ultimately favoring microbial
pathogenesis. How viral DUBs are particularly susceptible to environmental exposures, such as
ROS and chemical pollutants, have not been adequately explored, especially as novel modulators
of human pathogenesis. As it pertains to the rapid global spread of SARS-CoV-2 and the
prevalence of COVID-19 disease in the U.S. population and worldwide, we will be focusing our
research goals on understanding 1) how the SARS-CoV-2 Plpro protease activity (cleavage of
pro-proteins, ubiquitin-, and ISG15-conjugated proteins) can be regulated by environmentally-
generated small molecules, and 2) identifying COVID-19 disease-relevant cellular targets of the
Plpro upon viral infection in human lung epithelial cells.
期刊论文(6)
专著(0)
科研奖励(0)
会议论文
DOI:
10.7554/elife.41426
发表时间:
2018-11-13
期刊:
eLife
影响因子:
7.7
作者:
[Tonzi P, Yin Y, Lee CWT, Rothenberg E, Huang TT]
通讯作者:
Huang TT
How SUMOylation Fine-Tunes the Fanconi Anemia DNA Repair Pathway.
SUMOylation 如何微调范可尼贫血 DNA 修复途径。
DOI:
10.3389/fgene.2016.00061
发表时间:
2016
期刊:
Frontiers in genetics
影响因子:
3.7
作者:
[Coleman KE, Huang TT]
通讯作者:
Huang TT
DOI:
10.1016/j.dnarep.2019.03.016
发表时间:
2019-06
期刊:
DNA repair
影响因子:
3.8
作者:
[Peter Tonzi;Tony T. Huang]
通讯作者:
Peter Tonzi;Tony T. Huang
Defining the molecular basis of oncogene-induced replication stress
-
批准号:10515661
-
项目类别:
-
资助金额:$43.38万
-
财政年份:2021
-
负责人:Tony Tung Huang
-
依托单位:
Defining the molecular basis of oncogene-induced replication stress
-
批准号:10330467
-
项目类别:
-
资助金额:$44.1万
-
财政年份:2021
-
负责人:Tony Tung Huang
-
依托单位:
Understanding the mechanistic role of genome stability pathways in regulating cell homeostasis
-
批准号:10393487
-
项目类别:
-
资助金额:$42.38万
-
财政年份:2021
-
负责人:Tony Tung Huang
-
依托单位:
Understanding the mechanistic role of genome stability pathways in regulating cell homeostasis
-
批准号:10574614
-
项目类别:
-
资助金额:$42.38万
-
财政年份:2021
-
负责人:Tony Tung Huang
-
依托单位:
Mechanisms of reversible DUB oxidation in genome stability pathways
-
批准号:8857706
-
项目类别:
-
资助金额:$38.14万
-
财政年份:2015
-
负责人:Tony Tung Huang
-
依托单位:
Mechanisms of reversible DUB oxidation in genome stability pathways
-
批准号:9335360
-
项目类别:
-
资助金额:$38.14万
-
财政年份:2015
-
负责人:Tony Tung Huang
-
依托单位:
Mechanisms of reversible DUB oxidation in genome stability pathways
-
批准号:9751294
-
项目类别:
-
资助金额:$38.14万
-
财政年份:2015
-
负责人:Tony Tung Huang
-
依托单位:
Mechanisms of reversible DUB oxidation in genome stability pathways
-
批准号:9145183
-
项目类别:
-
资助金额:$38.14万
-
财政年份:2015
-
负责人:Tony Tung Huang
-
依托单位:
Role of Deubiquitination in Fanconi Anemia Cancer Susceptibility Pathway
-
批准号:8667129
-
项目类别:
-
资助金额:$29.43万
-
财政年份:2013
-
负责人:Tony Tung Huang
-
依托单位:
Role of Deubiquitination in Fanconi Anemia Cancer Susceptibility Pathway
-
批准号:8006429
-
项目类别:
-
资助金额:$34.06万
-
财政年份:2009
-
负责人:Tony Tung Huang
-
依托单位:
Role of Deubiquitination in Fanconi Anemia Cancer Susceptibility Pathway
-
批准号:7922972
-
项目类别:
-
资助金额:$21.23万
-
财政年份:2009
-
负责人:Tony Tung Huang
-
依托单位:
Role of Deubiquitination in Fanconi Anemia Cancer Susceptibility Pathway
-
批准号:7753878
-
项目类别:
-
资助金额:$34.4万
-
财政年份:2009
-
负责人:Tony Tung Huang
-
依托单位:
Role of Deubiquitination in Fanconi Anemia Cancer Susceptibility Pathway
-
批准号:8205032
-
项目类别:
-
资助金额:$34.06万
-
财政年份:2009
-
负责人:Tony Tung Huang
-
依托单位:
Role of Deubiquitination in Fanconi Anemia Cancer Susceptibility Pathway
-
批准号:8403008
-
项目类别:
-
资助金额:$32.86万
-
财政年份:2009
-
负责人:Tony Tung Huang
-
依托单位:
Role of Deubiquitination in Fanconi Anemia Cancer Susceptibility Pathway
-
批准号:8017207
-
项目类别:
-
资助金额:$6.99万
-
财政年份:2009
-
负责人:Tony Tung Huang
-
依托单位:
海外基金