@article{3ac660aa98b9470eb86a807df3e32161,
title = "Ubiquitin turnover and endocytic trafficking in yeast are regulated by ser57 phosphorylation of ubiquitin",
abstract = "Despite its central role in protein degradation little is known about the molecular mechanisms that sense, maintain, and regulate steady state concentration of ubiquitin in the cell. Here, we describe a novel mechanism for regulation of ubiquitin homeostasis that is mediated by phosphorylation of ubiquitin at the Ser57 position. We find that loss of Ppz phosphatase activity leads to defects in ubiquitin homeostasis that are at least partially attributable to elevated levels of Ser57 phosphorylated ubiquitin. Phosphomimetic mutation at the Ser57 position of ubiquitin conferred increased rates of endocytic trafficking and ubiquitin turnover. These phenotypes are associated with bypass of recognition by endosome-localized deubiquitylases - including Doa4 which is critical for regulation of ubiquitin recycling. Thus, ubiquitin homeostasis is significantly impacted by the rate of ubiquitin flux through the endocytic pathway and by signaling pathways that converge on ubiquitin itself to determine whether it is recycled or degraded in the vacuole.",
author = "Sora Lee and Tumolo, {Jessica M.} and Ehlinger, {Aaron C.} and Jernigan, {Kristin K.} and Qualls-Histed, {Susan J.} and Hsu, {Pi Chiang} and McDonald, {W. Hayes} and Chazin, {Walter J.} and MacGurn, {Jason A.}",
note = "Funding Information: We are very grateful to D Finley, M Boselli, R Piper, W Tansey, C Howard, S Wente, T Dawson, T Graham, and P Xu for yeast strains and reagents. We are very grateful to B Brasher for supplying the a-pSer57 antibody used in these studies. We thank Dr. Markus Voehler for technical support for the NMR experiments. We acknowledge M Smolka and K Rose for helpful advice regarding technical aspects and analysis of quantitative proteomic data. We thank T Graham and W Tansey for critical reading of this manuscript. We are especially grateful to S Emr for critical feedback and sage advice. We are grateful to E MacGurn for assistance with graphic design. JMT is funded by NIH training grant T32 CA119925. SL was supported by NIH training grant T32 HL069765. ACE was supported by NIH training grant T32 CA009582. This research was supported by NIH grant R00 GM101077 (to JAM), NIH grant R01 GM118491 (to JAM) and by NIH grant R35 GM118089 (to WJC). The NMR instrumentation was supported in part by grants from the NSF (0922862), NIH (S10 RR025677) and Vanderbilt University matching funds. This research was conducted while JAM was an AFAR Research Grant recipient from the American Federation for Aging Research. Funding Information: We are very grateful to D Finley, M Boselli, R Piper, W Tansey, C Howard, S Wente, T Dawson, T Graham, and P Xu for yeast strains and reagents. We are very grateful to B Brasher for supplying the a-pSer57 antibody used in these studies. We thank Dr. Markus Voehler for technical support for the NMR experiments. We acknowledge M Smolka and K Rose for helpful advice regarding technical aspects and analysis of quantitative proteomic data. We thank T Graham and W Tansey for critical reading of this manuscript. We are especially grateful to S Emr for critical feedback and sage advice. We are grateful to E MacGurn for assistance with graphic design. JMT is funded by NIH training grant T32 CA119925. SL was supported by NIH training grant T32 HL069765. ACE was supported by NIH training grant T32 CA009582. This research was supported by NIH grant R00 GM101077 (to JAM), NIH grant R01 GM118491 (to JAM) and by NIH grant R35 GM118089 (to WJC). The NMR instrumentation was supported in part by grants from the NSF (0922862), NIH (S10 RR025677) and Vanderbilt University matching funds. This research was conducted while JAM was an AFAR Research Grant recipient from the American Federation for Aging Research. National Institute of General Medical Sciences R00 GM101077 Jason A MacGurn. National Institute of General Medical Sciences R01 GM118491 Jason A MacGurn. National Institute of General Medical Sciences R35 GM118089 Walter J Chazin National Heart, Lung, and Blood Institute T32 HL069765 Sora Lee. National Cancer Institute T32 CA119925 Jessica M Tumolo.National Cancer Institute T32 CA009582 Aaron C Ehlinger. Publisher Copyright: {\textcopyright} Lee et al.",
year = "2017",
month = nov,
day = "13",
doi = "10.7554/eLife.29176",
language = "English (US)",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}