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中国神经科学学会第十届全国学术会议

作者： Zheng WEN Yang SHU Cai-Yun GAO Xue-Min Wang Guang-Jian QI Pei ZHANG Man LI Jing SHI Bo TIAN Department of Neurobiology Tongji Medical SchoolHuazhong University of Science and Technology Department of Neurobiology Southern Medical University

Objective raf kinase inhibitor protein(RKIP) is a major negative mediator of the ERK/MAPK *** downregulation of RKIP is correlated with many cancers,but the mechanisms that underbe this downregulation and its roles in the nervous system remain *** The phosphorylation of RKIP by CDK5 was confirmed by in vitro phosphorylation assays,site-directed point mutagenesis and a specific phosphorylation *** Effects of RKIP phosphorylation on its degradation and the activity of ERK/MAPK pathway were determined with regard to immunoprecipitation,GST pull-down assays,lysosome binding plus uptake assay,luciferase reporter assay,cell survival assay and cell cycle *** role of RKIP phosphorylation in Parkinson’s disease was measured in both MPP-induced cell model and MPTP-induced or transgenic animal *** Here,we demonstrate that RKIP is a substrate of cyclin-dependent kinase 5(CDK5) in neurons and that the phosphorylation of RKIP at T42 causes the release of ***,T42 phosphorylation promotes the exposure and recognition of the target motif "KLYEQ" in C-terminus of RKIP by chaperone Hsc70 and the subsequent degradation of RKIP via chaperone-mediated autophagy(CMA).Furthermore,in both MPTP-induced and transgenic models of Parkinson’s disease(PD),we demonstrate that CDK5-mediated phosphorylation and autophagy of RKIP is involved in the overactivation of the ERK/MAPK cascade,leading to S-phase re-entry and neuronal *** These findings provide evidence for the role of the CDK5/RKIP/ERK pathway in PD pathogenesis and suggest that this pathway may be a suitable therapeutic target in PD.

关键词： Parkinson’s diseases CDK5 raf kinase inhibitor protein protein phosphorylation chaperone-mediated autophagy

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Urothelial bladder cancer progression: lessons learned from the bench

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Journal of Cancer Metastasis and Treatment 2015年第1期1卷 57-66页

作者： Julieta P.Afonso Rui Freitas Francisco Lobo António Morais Jorge Oliveira Teresina Amaro Rui M.Reis Fátima M.Baltazar Adhemar Longatto-Filho Lúcio L.Santos Life and Health Sciences Research Institute(ICVS) School of Health SciencesUniversity of MinhoCampus de Gualtar4710-057 BragaPortugal ICVS/3B’s-PT Government Associate Laboratory 4806-909 Braga/GuimarãesPortugal Department of Urology Portuguese Institute of OncologyRua Dr.António Bernardino de Almeida4200-072 PortoPortugal Experimental Pathology and Therapeutics Research Center Portuguese Institute of OncologyRua Dr.António Bernardino de Almeida4200-072 PortoPortugal Molecular Oncology Research Center Barretos Cancer HospitalCEP 14784-400 BarretosSão PauloBrazil Laboratory of Medical Investigation(LIM 14) Faculty of MedicineSão Paulo State UniversityCEP 01246-000São PauloBrazil Department of Surgical Oncology Portuguese Institute of OncologyRua Dr.António Bernardino de Almeida4200-072 PortoPortugal Faculty of Health Sciences University Fernando PessoaRua Carlos da Maia4200-150 PortoPortugal.

Urothelial bladder carcinoma(UBC)is an intricate malignancy with a variable natural history and clinical *** developments in diagnosis/prognosis refi nement and treatment modalities,the recurrence rate is high,and progression from non-muscle to muscle invasive UBC commonly leads to ***,patients with muscle-invasive or extra-vesical disease often fail the standard chemotherapy treatment,and overall survival rates are ***,UBC remains a challenge in the oncology fi eld,representing an ideal candidate for research on biomarkers that could identify patients at increased risk of recurrence,progression,and ***,progress toward personalized medicine has been hampered by the unique genetic complexity of *** genome-wide expression and sequencing studies have brought new insights into its molecular features,pathogenesis and clinical diversity,revealing a landscape where classical pathology is intersected by the novel and heterogeneous molecular ***,it seems plausible to postulate that only an integrated signature of prognostic/predictive biomarkers inherent in different cancer hallmarks will reach clinical *** this review,we have summarized ours and others’research into novel putative biomarkers of progression and chemoresistance that encompass several hallmarks of cancer:tumor neovascularization,invasion and metastasis,and energy metabolism reprogramming of the tumor microenvironment.

关键词： CD147 lymphovascular invasion mammalian target of rapamycin monocarboxylate transporters progression raf kinase inhibitor protein scoring system urothelial bladder cancer

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