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Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo
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نویسنده
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odajima j. ,saini s. ,jung p. ,ndassa-colday y. ,ficaro s. ,geng y. ,marco e. ,michowski w. ,wang y.e. ,decaprio j.a. ,litovchick l. ,marto j. ,sicinski p.
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منبع
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plos genetics - 2016 - دوره : 12 - شماره : 11
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چکیده
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E-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. © 2016 odajima et al.
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آدرس
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department of cancer biology,dana-farber cancer institute,boston,ma,united states,department of genetics,harvard medical school,boston,ma, United States, department of internal medicine and massey cancer center,virginia commonwealth university,richmond,va, United States, department of cancer biology,dana-farber cancer institute,boston,ma,united states,department of genetics,harvard medical school,boston,ma, United States, department of cancer biology,dana-farber cancer institute,boston,ma,united states,department of biochemistry and molecular pharmacology,harvard medical school,boston,ma, United States, department of cancer biology,dana-farber cancer institute,boston,ma,united states,department of biochemistry and molecular pharmacology,harvard medical school,boston,ma, United States, department of cancer biology,dana-farber cancer institute,boston,ma,united states,department of genetics,harvard medical school,boston,ma, United States, department of biostatistics and computational biology,dana-farber cancer institute and harvard t.h. chan school of public health,boston,ma, United States, department of cancer biology,dana-farber cancer institute,boston,ma,united states,department of genetics,harvard medical school,boston,ma, United States, center for cancer computational biology,dana-farber cancer institute,boston,ma, United States, department of medical oncology,dana-farber cancer institute,and department of medicine,harvard medical school,boston,ma, United States, department of internal medicine and massey cancer center,virginia commonwealth university,richmond,va, United States, department of cancer biology,dana-farber cancer institute,boston,ma,united states,department of biochemistry and molecular pharmacology,harvard medical school,boston,ma, United States, department of cancer biology,dana-farber cancer institute,boston,ma,united states,department of genetics,harvard medical school,boston,ma, United States
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Authors
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