Protein Kinase A Binds and Activates Heat Shock Factor 1

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dc.contributor.author Murshid, Ayesha en_US
dc.contributor.author Chou, Shiuh-Dih en_US
dc.contributor.author Prince, Thomas en_US
dc.contributor.author Zhang, Yue en_US
dc.contributor.author Bharti, Ajit en_US
dc.contributor.author Calderwood, Stuart K. en_US
dc.date.accessioned 2012-01-09T21:00:20Z
dc.date.available 2012-01-09T21:00:20Z
dc.date.issued 2010-11-9 en_US
dc.identifier.citation Murshid, Ayesha, Shiuh-Dih Chou, Thomas Prince, Yue Zhang, Ajit Bharti, Stuart K. Calderwood. "Protein Kinase A Binds and Activates Heat Shock Factor 1" PLoS ONE 5(11): e13830. (2010) en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://hdl.handle.net/2144/2974
dc.description.abstract BACKGROUND. Many inducible transcription factors are regulated through batteries of posttranslational modifications that couple their activity to inducing stimuli. We have studied such regulation of Heat Shock Factor 1 (HSF1), a key protein in control of the heat shock response, and a participant in carcinogenisis, neurological health and aging. As the mechanisms involved in the intracellular regulation of HSF1 in good health and its dysregulation in disease are still incomplete we are investigating the role of posttranslational modifications in such regulation. METHODOLOGY/PRINCIPAL FINDINGS. In a proteomic study of HSF1 binding partners, we have discovered its association with the pleiotropic protein kinase A (PKA). HSF1 binds avidly to the catalytic subunit of PKA, (PKAca) and becomes phosphorylated on a novel serine phosphorylation site within its central regulatory domain (serine 320 or S320), both in vitro and in vivo. Intracellular PKAca levels and phosphorylation of HSF1 at S320 were both required for HSF1 to be localized to the nucleus, bind to response elements in the promoter of an HSF1 target gene (hsp70.1) and activate hsp70.1 after stress. Reduction in PKAca levels by small hairpin RNA led to HSF1 exclusion from the nucleus, its exodus from the hsp70.1 promoter and decreased hsp70.1 transcription. Likewise, null mutation of HSF1 at S320 by alanine substitution for serine led to an HSF1 species excluded from the nucleus and deficient in hsp70.1 activation. CONCLUSIONS. These findings of PKA regulation of HSF1 through S320 phosphorylation add to our knowledge of the signaling networks converging on this factor and may contribute to elucidating its complex roles in the stress response and understanding HSF1 dysregulation in disease. en_US
dc.description.sponsorship National Institutes of Health (2RO1CA047407, RO1CA077465) en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.rights Murshid et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_US
dc.title Protein Kinase A Binds and Activates Heat Shock Factor 1 en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pone.0013830 en_US
dc.identifier.pubmedid 21085490 en_US
dc.identifier.pmcid 2976705 en_US

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