Odajima, JunkoSaini, SiddharthJung, PiotrNdassa-Colday, YasmineFicaro, ScottGeng, YanMarco, EugenioMichowski, WojciechWang, Yaoyu E.DeCaprio, JamesLitovchick, LarisaMarto, JarrodSicinski, Piotr2016-12-022016Odajima, J., S. Saini, P. Jung, Y. Ndassa-Colday, S. Ficaro, Y. Geng, E. Marco, et al. 2016. “Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo.” PLoS Genetics 12 (11): e1006429. doi:10.1371/journal.pgen.1006429. http://dx.doi.org/10.1371/journal.pgen.1006429.1553-7390http://nrs.harvard.edu/urn-3:HUL.InstRepos:29625999E-type cyclins (cyclins E1 and E2) are components of the cell cycle machinery that has been conserved from yeast to humans. The major function of E-type cyclins is to drive cell division. It is unknown whether in addition to their ‘core’ cell cycle functions, E-type cyclins also perform unique tissue-specific roles. Here, we applied high-throughput mass spectrometric analyses of mouse organs to define the repertoire of cyclin E protein partners in vivo. We found that cyclin E interacts with distinct sets of proteins in different compartments. These cyclin E interactors are highly enriched for phosphorylation targets of cyclin E and its catalytic partner, the cyclin-dependent kinase 2 (Cdk2). Among cyclin E interactors we identified several novel tissue-specific substrates of cyclin E-Cdk2 kinase. In proliferating compartments, cyclin E-Cdk2 phosphorylates Lin proteins within the DREAM complex. In the testes, cyclin E-Cdk2 phosphorylates Mybl1 and Dmrtc2, two meiotic transcription factors that represent key regulators of spermatogenesis. In embryonic and adult brains cyclin E interacts with proteins involved in neurogenesis, while in adult brains also with proteins regulating microtubule-based processes and microtubule cytoskeleton. We also used quantitative proteomics to demonstrate re-wiring of the cyclin E interactome upon ablation of Cdk2. This approach can be used to study how protein interactome changes during development or in any pathological state such as aging or cancer.en-USBiology and Life SciencesCell BiologyCell ProcessesCell Cycle and Cell DivisionCyclinsPrecipitation TechniquesImmunoprecipitationBiochemistryProteinsPost-Translational ModificationPhosphorylationAnatomyReproductive SystemGenital AnatomyTestesMedicine and Health SciencesPhysiologyImmune PhysiologySpleenMeiosisSpermatogenesisChromosome BiologyReproductive PhysiologyProtein InteractionsJournal Article2016-12-0210.1371/journal.pgen.1006429