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dc.contributor.authorMa, Jian
dc.contributor.authorGrant, Christopher E.
dc.contributor.authorPlagens, Rosemary N.
dc.contributor.authorBarrett, Lindsey N.
dc.contributor.authorGuisbert, Karen S. Kim
dc.contributor.authorGuisbert, Eric
dc.date.accessioned2017-06-13T14:11:58Z
dc.date.available2017-06-13T14:11:58Z
dc.date.issued2017-03
dc.identifier.citationMa, J., Grant, C. E., Plagens, R. N., Barrett, L. N., Guisbert, K. S., & Guisbert, E. (2017). Cellular Proteomes Drive Tissue-Specific Regulation of the Heat Shock Response. G3 Genes|Genomes|Genetics, 7(3), 1011-1018. doi:10.1534/g3.116.038232en_US
dc.identifier.urihttp://hdl.handle.net/11141/1522
dc.description.abstractThe heat shock response (HSR) is a cellular stress response that senses protein misfolding and restores protein folding homeostasis, or proteostasis. We previously identified an HSR regulatory network inCaenorhabditis elegans consisting of highly conserved genes that have important cellular roles in maintaining proteostasis. Unexpectedly, the effects of these genes on the HSR are distinctly tissue-specific. Here, we explore this apparent discrepancy and find that muscle-specific regulation of the HSR by the TRiC/CCT chaperonin is not driven by an enrichment of TRiC/CCT in muscle, but rather by the levels of one of its most abundant substrates, actin. Knockdown of actin subunits reduces induction of the HSR in muscle upon TRiC/CCT knockdown; conversely, overexpression of an actin subunit sensitizes the intestine so that it induces the HSR upon TRiC/CCT knockdown. Similarly, intestine-specific HSR regulation by the signal recognition particle (SRP), a component of the secretory pathway, is driven by the vitellogenins, some of the most abundant secretory proteins. Together, these data indicate that the specific protein folding requirements from the unique cellular proteomes sensitizes each tissue to disruption of distinct subsets of the proteostasis network. These findings are relevant for tissue-specific, HSR-associated human diseases such as cancer and neurodegenerative diseases. Additionally, we characterize organismal phenotypes of actin overexpression including a shortened lifespan, supporting a recent hypothesis that maintenance of the actin cytoskeleton is an important factor for longevity.en_US
dc.description.sponsorshipPublication of this article was funded in part by the Open Access Subvention Fund and the Florida Tech Libraries.
dc.language.isoen_USen_US
dc.rightsPublication of this article was funded in part by the Open Access Subvention Fund and the Florida Tech Libraries. Creative Commons Attribution 4.0 International Licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleCellular Proteomes Drive Tissue-Specific Regulation of the Heat Shock Responseen_US
dc.typeArticleen_US
dc.identifier.doi10.1534/g3.116.038232


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Publication of this article was funded in part by the Open Access Subvention Fund and the Florida Tech Libraries. Creative Commons Attribution 4.0 International License
Except where otherwise noted, this item's license is described as Publication of this article was funded in part by the Open Access Subvention Fund and the Florida Tech Libraries. Creative Commons Attribution 4.0 International License