STAT3 Regulation of Citrate Synthase Is Essential during the Initiation of Lymphocyte Cell Growth

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dc.contributor.authorMacPherson, Sarah
dc.contributor.authorHorkoff, Michael
dc.contributor.authorGravel, Cleo
dc.contributor.authorHoffmann, Thomas
dc.contributor.authorZuber, Johannes
dc.contributor.authorLum, Julian J.
dc.date.accessioned2018-02-26T17:50:58Z
dc.date.available2018-02-26T17:50:58Z
dc.date.copyright2017en_US
dc.date.issued2017
dc.description.abstractCitrate is a required carbon precursor for de novo fatty acid and membrane lipid synthesis. However, the pathways regulating intracellular citrate, particularly during the initial transition from a resting state to cell growth, remain unclear. Here, we show that STAT3 is among the first signaling events activated in resting lymphocytes following growth factor stimulation. During this period, the inhibition of STAT3 blocks the expression of citrate synthase (CS) and reduces the levels of intracellular citrate. As a consequence of CS loss and the reduction in citrate, cells are unable to grow or proliferate in response to extracellular growth factors. These effects were due to STAT3-dependent transcriptional regulation of CS, as exogenous addition of citrate could restore fatty acid synthesis, cell growth, and proliferation. Taken together, our studies reveal that transcription-dependent control of CS is essential for regulating the initiation of cell growth.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThe work in this manuscript was supported by (all to J.J.L.) the BC Cancer Foundation, the Cancer Research Society, and the Canadian Institutes of Health Research. S.M. was partially supported by a scholarship from the University of Victoria.en_US
dc.identifier.citationMacPherson, S., Horkoff, M., Gravel, C., Hoffmann, T., Zuber, J. & Lum, J.J. (2017). STAT3 Regulation of Citrate Synthase Is Essential during the Initiation of Lymphocyte Cell Growth. Cell Reports, 19(5), 910-918. https://doi.org/10.1016/j.celrep.2017.04.012en_US
dc.identifier.urihttp://dx.doi.org/10.1016/j.celrep.2017.04.012
dc.identifier.urihttp://hdl.handle.net/1828/9095
dc.language.isoenen_US
dc.publisherCell Reportsen_US
dc.subjectcitrate synthaseen_US
dc.subjectSTAT3en_US
dc.subjectcell growthen_US
dc.subjectcitrateen_US
dc.titleSTAT3 Regulation of Citrate Synthase Is Essential during the Initiation of Lymphocyte Cell Growthen_US
dc.typeArticleen_US

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