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dc.contributor.authorCohen, Shenhav Orit
dc.contributor.authorZhai, Bo
dc.contributor.authorGygi, Steven P.
dc.contributor.authorGoldberg, Alfred L.
dc.date.accessioned2013-04-30T20:13:45Z
dc.date.issued2012
dc.identifier.citationCohen, Shenhav, Bo Zhai, Steven P. Gygi, and Alfred L. Goldberg. 2012. Ubiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophy. The Journal of Cell Biology 198(4): 575-589.en_US
dc.identifier.issn0021-9525en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10594369
dc.description.abstractDuring muscle atrophy, myofibrillar proteins are degraded in an ordered process in which MuRF1 catalyzes ubiquitylation of thick filament components (Cohen et al. 2009. J. Cell Biol. http://dx.doi.org/10.1083/jcb.200901052). Here, we show that another ubiquitin ligase, Trim32, ubiquitylates thin filament (actin, tropomyosin, troponins) and Z-band (α-actinin) components and promotes their degradation. Down-regulation of Trim32 during fasting reduced fiber atrophy and the rapid loss of thin filaments. Desmin filaments were proposed to maintain the integrity of thin filaments. Accordingly, we find that the rapid destruction of thin filament proteins upon fasting was accompanied by increased phosphorylation of desmin filaments, which promoted desmin ubiquitylation by Trim32 and degradation. Reducing Trim32 levels prevented the loss of both desmin and thin filament proteins. Furthermore, overexpression of an inhibitor of desmin polymerization induced disassembly of desmin filaments and destruction of thin filament components. Thus, during fasting, desmin phosphorylation increases and enhances Trim32-mediated degradation of the desmin cytoskeleton, which appears to facilitate the breakdown of Z-bands and thin filaments.en_US
dc.language.isoen_USen_US
dc.publisherThe Rockefeller University Pressen_US
dc.relation.isversionofdoi:10.1083/jcb.201110067en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514026/pdf/en_US
dash.licenseLAA
dc.subjectArticleen_US
dc.titleUbiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophyen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalThe Journal of Cell Biologyen_US
dash.depositing.authorGygi, Steven P.
dc.date.available2013-04-30T20:13:45Z
dc.identifier.doi10.1083/jcb.201110067*
dash.contributor.affiliatedZhai, Bo
dash.contributor.affiliatedCohen, Shenhav Orit
dash.contributor.affiliatedGoldberg, Alfred
dash.contributor.affiliatedGygi, Steven


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