Ubiquitin turnover and endocytic trafficking in yeast are regulated by Ser57 phosphorylation of ubiquitin
- Vanderbilt University, United States
- Cornell University, United States
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.
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Author details
Funding
National Institute of General Medical Sciences (R00 GM101077)
- Jason A MacGurn
National Institute of General Medical Sciences (R01 GM118491)
- Jason A MacGurn
American Federation for Aging Research (Research Grants for Junior Faculty)
- 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
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Lee et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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