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dc.contributor.authorZhang, Yue
dc.contributor.authorMurshid, Ayesha
dc.contributor.authorPrince, Thomas
dc.contributor.authorCalderwood, Stuart K.
dc.date.accessioned2012-04-06T20:56:08Z
dc.date.issued2011
dc.identifier.citationZhang, Yue, Ayesha Murshid, Thomas Prince, and Stuart K. Calderwood. 2011. Protein kinase a regulates molecular chaperone transcription and protein aggregation. PLoS ONE 6(12): e29850.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8519284
dc.description.abstractHeat shock factor 1 (HSF1) regulates one of the major pathways of protein quality control and is essential for deterrence of protein-folding disorders, particularly in neuronal cells. However, HSF1 activity declines with age, a change that may open the door to progression of neurodegenerative disorders such as Huntington's disease. We have investigated mechanisms of HSF1 regulation that may become compromised with age. HSF1 binds stably to the catalytic domain of protein kinase A (PKAcα) and becomes phosphorylated on at least one regulatory serine residue (S320). We show here that PKA is essential for effective transcription of HSP genes by HSF1. PKA triggers a cascade involving HSF1 binding to the histone acetylase p300 and positive translation elongation factor 1 (p-TEFb) and phosphorylation of the c-terminal domain of RNA polymerase II, a key mechanism in the downstream steps of HSF1-mediated transcription. This cascade appears to play a key role in protein quality control in neuronal cells expressing aggregation-prone proteins with long poly-glutamine (poly-Q) tracts. Such proteins formed inclusion bodies that could be resolved by HSF1 activation during heat shock. Resolution of the inclusions was inhibited by knockdown of HSF1, PKAcα, or the pTEFb component CDK9, indicating a key role for the HSF1-PKA cascade in protein quality control.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0028950en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245242/en_US
dash.licenseLAA
dc.titleProtein Kinase A Regulates Molecular Chaperone Transcription and Protein Aggregationen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorZhang, Yue
dc.date.available2012-04-06T20:56:08Z
dc.identifier.doi10.1371/journal.pone.0028950*
dash.contributor.affiliatedZhang, Yue
dash.contributor.affiliatedCalderwood, Stuart
dash.contributor.affiliatedMurshid, Ayesha


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