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  • Cell Research
    Top 10 VOLUME 20 ISSUE 6 6 2010 614 621 New insights into p53 activation Christopher L Brooks 1 and Wei Gu 2 1 Stemline Therapeutics Inc 1675 York Avenue Suite 34 L New York NY 10128 USA 2 Institute for Cancer Genetics and Department of Pathology College of Physicians Surgeons Columbia University 1130 St Nicholas Ave New York NY 10032 USA Correspondence Christopher L Brooks Tel 212 531 5973 E mail cbrooks stemline com The tumor suppressor p53 is a multifunctional highly regulated and promoter specific transcriptional factor that is uniquely sensitive to DNA damage and cellular stress signaling The mechanisms by which p53 directs a damaged cell down either a cell growth arrest or an apoptotic pathway remain poorly understood Evidence suggests that the in vivo functions of p53 seem to balance the cell fate choice with the type and severity of damage that occurs The concept of antirepression or inhibition of factors that normally keep p53 at bay may help explain the physiological mechanisms for p53 activation These factors also provide novel chemotherapeutic targets for the reactivation of p53 in tumors harboring a wild type copy of the gene Cell Research 2010 20 614 621 doi 10

    Original URL path: http://www.cell-research.com/arts.asp?id=516 (2016-02-14)
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  • Cell Research
    Online Publication Current Issue Top 10 VOLUME 20 ISSUE 6 6 2010 622 630 Network models for molecular kinetics and their initial applications to human health Gregory R Bowman 1 Xuhui Huang 2 3 and Vijay S Pande 1 4 1 Biophysics Program Stanford University Stanford CA 94305 USA 2 Department of Chemistry The Hong Kong University of Science and Technology Kowloon Hong Kong 3 Department of Bioengineering Stanford University Stanford CA 94305 USA 4 Department of Chemistry Stanford University Stanford CA 94305 USA Correspondence Vijay S Pande E mail pande stanford edu Molecular kinetics underlies all biological phenomena and like many other biological processes may best be understood in terms of networks These networks called Markov state models MSMs are typically built from physical simulations Thus they are capable of quantitative prediction of experiments and can also provide an intuition for complex conformational changes Their primary application has been to protein folding however these technologies and the insights they yield are transferable For example MSMs have already proved useful in understanding human diseases such as protein misfolding and aggregation in Alzheimer s disease Cell Research 2010 20 622 630 doi 10 1038 cr 2010 57 published online 27 April

    Original URL path: http://www.cell-research.com/arts.asp?id=517 (2016-02-14)
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  • Cell Research
    Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx NY 10461 USA 2 The Center for Autoimmune and Musculoskeletal Disease The Feinstein Institute for Medical Research Manhasset NY 11030 USA 3 Departments of Medicine and Pathology Weill Cornell College of Medicine New York NY 10021 USA 4 Department of Cancer Biology Dana Farber Cancer Institute and Department of Pathology Harvard Medical School Boston MA 02115 USA 5 Current address Department of Anatomy and Cell Biology University of Kansas Medical Center Kansas City KS 66160 USA Correspondence B Hilda Ye Tel 1 718 430 3339 E mail hilda ye einstein yu edu Germinal centers GC of secondary lymphoid tissues are critical to mounting a high affinity humoral immune response B cells within the GC undergo rapid clonal expansion and selection while diversifying their antibody genes Although it is generally believed that GC B cells employ a unique proliferative program to accommodate these processes little is known about how the GC associated cell cycle is orchestrated The D type cyclins constitute an important component of the cell cycle engine that enables the cells to respond to physiological changes Cell type and developmental stage specific roles of D type cyclins have been described but the cyclin D requirement during GC reaction has not been addressed In this study we report that cyclin D3 is largely dispensable for proliferation and Ig class switching of in vitro activated B cells In contrast GC development in Ccnd3 mice is markedly impaired as is the T cell dependent antibody response Within the GC although both switched and unswitched B cells are affected by cyclin D3 inactivation the IgM pool is more severely reduced Interestingly despite a compensatory increase in cyclin D2 expression a significant number of Ccnd3 GC B cells accumulate in quiescent G0 state Lastly

    Original URL path: http://www.cell-research.com/arts.asp?id=518 (2016-02-14)
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  • Cell Research
    Membranaires Normales et Pathologiques Centre National de la Recherche Scientifique UMR 5235 Universit Montpellier II Montpellier France 4 D閜artement des microscopies plate forme RIO INSERM U966 Universit Fran鏾is Rabelais Tours France 5 Centre for Molecular Microbiology and Infection and Division of Cell and Molecular Biology Imperial College London London SW7 2AZ UK Correspondence Agnès Wiedemann Tel 33 2 47 42 78 70 E mail awiedemann tours inra fr Salmonella can invade non phagocytic cells through its type III secretion system T3SS 1 which induces a Trigger entry process This study showed that Salmonella enterica subspecies enterica serovar Enteritidis can also invade cells via the Rck outer membrane protein Rck was necessary and sufficient to enable non invasive E coli and Rck coated beads to adhere to and invade different cells Internalization analysis of latex beads coated with different Rck peptides showed that the peptide containing amino acids 140 150 promoted adhesion whereas amino acids between 150 and 159 modulated invasion Expression of dominant negative derivatives and use of specific inhibitors demonstrated the crucial role of small GTPases Rac1 and Cdc42 in activating the Arp2 3 complex to trigger formation of actin rich accumulation leading to Rck dependent internalization Finally scanning

    Original URL path: http://www.cell-research.com/arts.asp?id=519 (2016-02-14)
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  • Cell Research
    401 444 8402 E mail timothy kinsella case edu DNA mismatch repair MMR processes the chemically induced mispairs following treatment with clinically important nucleoside analogs such as 6 thioguanine 6 TG and 5 fluorouracil 5 FU MMR processing of these drugs has been implicated in activation of a prolonged G2 M cell cycle arrest for repair and later induction of apoptosis and or autophagy for irreparable DNA damage In this study we investigated the role of B cl2 and adenovirus E1B N ineteen kilodalton I nteracting P rotein BNIP3 in the activation of autophagy and the temporal relationship between a G2 M cell cycle arrest and the activation of BNIP3 mediated autophagy following MMR processing of 6 TG and 5 FU We found that BNIP3 protein levels are upregulated in a MLH1 MMR dependent manner following 6 TG and 5 FU treatment Subsequent small interfering RNA siRNA mediated BNIP3 knockdown abrogates 6 TG induced autophagy We also found that p53 knockdown or inhibition of mTOR activity by rapamycin cotreatment impairs 6 TG and 5 FU induced upregulation of BNIP3 protein levels and autophagy Furthermore suppression of Checkpoint kinase 1 Chk1 expression with a subsequent reduction in 6 TG induced G2

    Original URL path: http://www.cell-research.com/arts.asp?id=520 (2016-02-14)
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  • Cell Research
    Zhang 1 Jin Wang 1 Ke Zen 1 Yang Xiang 1 Dongjin Wang 2 and Chen Yu Zhang 1 1 Jiangsu Diabetes Center State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University Nanjing 210093 China 2 Department of Thoracic Surgery The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 China 3 Department of Physiology University of Toronto Toronto Ontario M5S 1A8 Canada Correspondence Chen Yu Zhang Dongjin Wang Yang Xiang E mail cyzhang nju edu cn gldjw 163 com xiangy nju edu cn PGC 1α a potent transcriptional coactivator is the major regulator of mitochondrial biogenesis and activity in the cardiac muscle The dysregulation of PGC 1α and its target genes has been reported to be associated with congenital and acquired heart diseases By examining myocardium samples from patients with Tetralogy of Fallot we show here that PGC 1α expression levels are markedly increased in patients compared with healthy controls and positively correlated with the severity of cyanosis Furthermore hypoxia significantly induced the expression of PGC 1α and mitochondrial biogenesis in cultured cardiac myocytes Mechanistic studies suggest that hypoxia induced PGC 1α expression is regulated through the AMPK signaling pathway Together our data indicate

    Original URL path: http://www.cell-research.com/arts.asp?id=521 (2016-02-14)
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  • Cell Research
    1 Haoni Li 1 Hongya Gu 1 2 and Li Jia Qu 1 2 1 National Laboratory for Protein Engineering and Plant Genetic Engineering College of Life Sciences Peking University Beijing 100871 China 2 The National Plant Gene Research Center Beijing Beijing 100101 China Correspondence Li Jia Qu Tel 86 10 6275 1841 E mail qulj pku edu cn 1 Deoxy D xylulose 5 phosphate reductoisomerase DXR is an important enzyme involved in the 2 C methyl D erythritol 4 phosphate MEP pathway which provides the basic five carbon units for isoprenoid biosynthesis To investigate the role of the MEP pathway in plant development and metabolism we carried out detailed analyses on a dxr mutant GK 215C01 and two DXR transgenic co suppression lines OX DXR L2 and OX DXR L7 We found that the dxr mutant was albino and dwarf It never bolted had significantly reduced number of trichomes and most of the stomata could not close normally in the leaves The two co suppression lines produced more yellow inflorescences and albino sepals with no trichomes The transcription levels of genes involved in trichome initiation were found to be strongly affected including GLABRA1 TRANSPARENT TESTA GLABROUS 1 TRIPTYCHON and SPINDLY expression of which is regulated by gibberellic acids GAs Exogenous application of GA 3 could partially rescue the dwarf phenotype and the trichome initiation of dxr whereas exogenous application of abscisic acid ABA could rescue the stomata closure defect suggesting that lower levels of both GA and ABA contribute to the phenotype in the dxr mutants We further found that genes involved in the biosynthetic pathways of GA and ABA were coordinately regulated These results indicate that disruption of the plastidial MEP pathway leads to biosynthetic deficiency of photosynthetic pigments GAs and ABA and thus the developmental abnormalities and

    Original URL path: http://www.cell-research.com/arts.asp?id=522 (2016-02-14)
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  • Cell Research
    Wei 1 Rong Xiang 1 and Yue Wang 1 1 School of Medicine Nankai University Tianjin 300071 China 2 Tianjin Medical University Tianjin Cancer Hospital Tianjin 300060 China Correspondence Yue Wang Tel 086 022 23499550 E mail wangyue nankai edu cn The tumor microenvironment TME plays a prominent role in the growth of tumor cells As the major inflammatory component of the TME M2d macrophages are educated by the TME such that they adopt an immunosuppressive role that promotes tumor metastasis and progression Fra 1 forms activator protein 1 heterodimers with Jun partners and drives gene transcription Fra 1 is thought to drastically induce tumorigenesis and progression However the functional role of Fra 1 in the generation of M2d macrophages is poorly understood to date Here we demonstrate that 4T1 mammary carcinoma cells when co cultured with RAW264 7 macrophage cells skew the RAW264 7 macrophage cell differentiation into M2d macrophages The 4T1 cells stimulate de novo overexpression of Fra 1 in RAW264 7 cells and then Fra 1 binds to the interleukin 6 IL 6 promoter to increase the production of the cytokine IL 6 in RAW264 7 cells IL 6 acts in an autocrine fashion to skew RAW264

    Original URL path: http://www.cell-research.com/arts.asp?id=523 (2016-02-14)
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