title: Quantification of protein half-lives in the budding yeast proteome.
abstract: A complete description of protein metabolism requires knowledge of the rates of protein production and destruction within cells. Using an epitope-tagged strain collection, we measured the half-life of >3,750 proteins in the yeast proteome after inhibition of translation. By integrating our data with previous measurements of protein and mRNA abundance and translation rate, we provide evidence that many proteins partition into one of two regimes for protein metabolism: one optimized for efficient production or a second optimized for regulatory efficiency. Incorporation of protein half-life information into a simple quantitative model for protein production improves our ability to predict steady-state protein abundance values. Analysis of a simple dynamic protein production model reveals a remarkable correlation between transcriptional regulation and protein half-life within some groups of coregulated genes, suggesting that cells coordinate these two processes to achieve uniform effects on protein abundances. Our experimental data and theoretical analysis underscore the importance of an integrative approach to the complex interplay between protein degradation, transcriptional regulation, and other determinants of protein metabolism.
authors.affiliation: Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, 94143-2240, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Belle
authors.forename: Amos
authors.initials: A
authors.lastname: Tanay
authors.forename: Ledion
authors.initials: L
authors.lastname: Bitincka
authors.forename: Ron
authors.initials: R
authors.lastname: Shamir
authors.forename: Erin K
authors.initials: EK
authors.lastname: O'Shea
mesh_terms: D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006207:Half-Life; D008954:Models, Biological; D040081:Protein Array Analysis; D021381:Protein Transport; D020543:Proteome / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D004718:Saccharomycetales / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D020543:Proteome; D012333:RNA, Messenger