Person: Geng, Yan
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Geng
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Yan
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Geng, Yan
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Publication Cyclin D-CDK4 kinase destabilizes PD-L1 via Cul3SPOP to control cancer immune surveillance(2017) Zhang, Jinfang; Bu, Xia; Wang, Haizhen; Zhu, Yasheng; Geng, Yan; Nihira, Naoe; Tan, Yuyong; Ci, Yanpeng; Wu, Fei; Dai, Xiangpeng; Guo, Jianping; Huang, Yu-Han; Fan, Caoqi; Ren, Shancheng; Sun, Yinghao; Freeman, Gordon; Sicinski, Piotr; Wei, WenyiPublication Mammalian E-type Cyclins Control Chromosome Pairing, Telomere Stability and CDK2 Localization in Male Meiosis(Public Library of Science, 2014) Martinerie, Laetitia; Manterola, Marcia; Chung, Sanny S. W.; Panigrahi, Sunil K.; Weisbach, Melissa; Vasileva, Ana; Geng, Yan; Sicinski, Peter; Wolgemuth, Debra J.Loss of function of cyclin E1 or E2, important regulators of the mitotic cell cycle, yields viable mice, but E2-deficient males display reduced fertility. To elucidate the role of E-type cyclins during spermatogenesis, we characterized their expression patterns and produced additional deletions of Ccne1 and Ccne2 alleles in the germline, revealing unexpected meiotic functions. While Ccne2 mRNA and protein are abundantly expressed in spermatocytes, Ccne1 mRNA is present but its protein is detected only at low levels. However, abundant levels of cyclin E1 protein are detected in spermatocytes deficient in cyclin E2 protein. Additional depletion of E-type cyclins in the germline resulted in increasingly enhanced spermatogenic abnormalities and corresponding decreased fertility and loss of germ cells by apoptosis. Profound meiotic defects were observed in spermatocytes, including abnormal pairing and synapsis of homologous chromosomes, heterologous chromosome associations, unrepaired double-strand DNA breaks, disruptions in telomeric structure and defects in cyclin-dependent-kinase 2 localization. These results highlight a new role for E-type cyclins as important regulators of male meiosis.Publication p600 Plays Essential Roles in Fetal Development(Public Library of Science, 2013) Nakaya, Takeo; Ishiguro, Kei-ichiro; Belzil, Camille; Rietsch, Anna M.; Yu, Qunyan; Mizuno, Shin-ichi; Bronson, Roderick; Geng, Yan; Nguyen, Minh Dang; Akashi, Koichi; Sicinski, Piotr; Nakatani, Yoshihiro Patp600 is a multifunctional protein implicated in cytoskeletal organization, integrin-mediated survival signaling, calcium-calmodulin signaling and the N-end rule pathway of ubiquitin-proteasome-mediated proteolysis. While push, the Drosophila counterpart of p600, is dispensable for development up to adult stage, the role of p600 has not been studied during mouse development. Here we generated p600 knockout mice to investigate the in vivo functions of p600. Interestingly, we found that homozygous deletion of p600 results in lethality between embryonic days 11.5 and 13.5 with severe defects in both embryo and placenta. Since p600 is required for placental development, we performed conditional disruption of p600, which deletes selectively p600 in the embryo but not in the placenta. The conditional mutant embryos survive longer than knockout embryos but ultimately die before embryonic day 14.5. The mutant embryos display severe cardiac problems characterized by ventricular septal defects and thin ventricular walls. These anomalies are associated with reduced activation of FAK and decreased expression of MEF2, which is regulated by FAK and plays a crucial role in cardiac development. Moreover, we observed pleiotropic defects in the liver and brain. In sum, our study sheds light on the essential roles of p600 in fetal development.Publication Differences in regulation and function of E-cyclins in human cancer cells(Landes Bioscience, 2013) Geng, Yan; Sicinski, PiotrPublication Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo(Public Library of Science, 2016) Odajima, Junko; Saini, Siddharth; Jung, Piotr; Ndassa-Colday, Yasmine; Ficaro, Scott; Geng, Yan; Marco, Eugenio; Michowski, Wojciech; Wang, Yaoyu E.; DeCaprio, James; Litovchick, Larisa; Marto, Jarrod; Sicinski, PiotrE-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.