Person: Dephoure, Noah Elias
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Dephoure
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Noah Elias
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Dephoure, Noah Elias
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Publication PP2ARts1 is a master regulator of pathways that control cell size(The Rockefeller University Press, 2014) Zapata, Jessica; Dephoure, Noah Elias; MacDonough, Tracy; Yu, Yaxin; Parnell, Emily J.; Mooring, Meghan; Gygi, Steven; Stillman, David J.; Kellogg, Douglas R.Cell size checkpoints ensure that passage through G1 and mitosis occurs only when sufficient growth has occurred. The mechanisms by which these checkpoints work are largely unknown. PP2A associated with the Rts1 regulatory subunit (PP2ARts1) is required for cell size control in budding yeast, but the relevant targets are unknown. In this paper, we used quantitative proteome-wide mass spectrometry to identify proteins controlled by PP2ARts1. This revealed that PP2ARts1 controls the two key checkpoint pathways thought to regulate the cell cycle in response to cell growth. To investigate the role of PP2ARts1 in these pathways, we focused on the Ace2 transcription factor, which is thought to delay cell cycle entry by repressing transcription of the G1 cyclin CLN3. Diverse experiments suggest that PP2ARts1 promotes cell cycle entry by inhibiting the repressor functions of Ace2. We hypothesize that control of Ace2 by PP2ARts1 plays a role in mechanisms that link G1 cyclin accumulation to cell growth.Publication Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast(eLife Sciences Publications, Ltd, 2014) Dephoure, Noah Elias; Hwang, Sunyoung; O'Sullivan, Ciara; Dodgson, Stacie E; Gygi, Steven; Amon, Angelika; Torres, Eduardo MAneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive oxygen species (ROS). Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains. Our results show that aneuploidy causes alterations in metabolism and redox homeostasis. Cells respond to these alterations through both transcriptional and posttranscriptional mechanisms. DOI: http://dx.doi.org/10.7554/eLife.03023.001Publication SIRT4 controls the balance between lipid synthesis and catabolism by repressing malonyl-CoA decarboxylase(BioMed Central, 2012) Laurent, Gaëlle; German, Natalie Janelle; Saha, Asish K; de Boer, Vincent CJ; Fischer, Frank; Boanca, Gina; Dephoure, Noah Elias; Vaitheesvaran, Bhavapriya; Davies, Michael; Gygi, Steven; Muoio, Deborah M; Kurland, Irwin J; Steegborn, Clemens; Ruderman, Neil B; Haigis, Marcia