title: Proteome half-life dynamics in living human cells.
abstract: Cells remove proteins by two processes: degradation and dilution due to cell growth. The balance between these basic processes is poorly understood. We addressed this by developing an accurate and noninvasive method for measuring protein half-lives, called "bleach-chase," that is applicable to fluorescently tagged proteins. Assaying 100 proteins in living human cancer cells showed half-lives that ranged between 45 minutes and 22.5 hours. A variety of stresses that stop cell division showed the same general effect: Long-lived proteins became longer-lived, whereas short-lived proteins remained largely unaffected. This effect is due to the relative strengths of degradation and dilution and suggests a mechanism for differential killing of rapidly growing cells by growth-arresting drugs. This approach opens a way to understand proteome half-life dynamics in living cells.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. eraneden@gmail.com
authors.forename: Eran
authors.initials: E
authors.lastname: Eden
authors.forename: Naama
authors.initials: N
authors.lastname: Geva-Zatorsky
authors.forename: Irina
authors.initials: I
authors.lastname: Issaeva
authors.forename: Ariel
authors.initials: A
authors.lastname: Cohen
authors.forename: Erez
authors.initials: E
authors.lastname: Dekel
authors.forename: Tamar
authors.initials: T
authors.lastname: Danon
authors.forename: Lydia
authors.initials: L
authors.lastname: Cohen
authors.forename: Avi
authors.initials: A
authors.lastname: Mayo
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D005453:Fluorescence; D006207:Half-Life; D006801:Humans; D008027:Light; D008164:Luminescent Proteins; D008856:Microscopy, Fluorescence; D011506:Proteins / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D013312:Stress, Physiological; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D008164:Luminescent Proteins; D011506:Proteins; D020543:Proteome; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D002166:Camptothecin