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Monitoring development of chemoresistance to cyclin-dependent kinases inhibition by two-dimensional liquid phase protein fractionation
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SYSNO ASEP 0042104 Document Type C - Proceedings Paper (int. conf.) R&D Document Type Conference Paper Title Monitoring development of chemoresistance to cyclin-dependent kinases inhibition by two-dimensional liquid phase protein fractionation Title Sledování vzniku chemorezistence k inhibici cyklin-dependentních kináz pomocí dvojrozměrné kapalinové separace proteinů Author(s) Skalníková, Helena (UZFG-Y) RID, ORCID
Halada, Petr (MBU-M) RID, ORCID
Hajdúch, M. (CZ)
Vydra, D. (CZ)
Dzubak, P. (CZ)
Dziechciarková, M. (CZ)
Strnad, M. (CZ)
Kovářová, Hana (UZFG-Y) RID, ORCIDSource Title Third Annual European Symposium on Protein Fractionation and Biomarker Discovery. - Oxford : Worcester College, 2006 Pages s. 1 Number of pages 1 s. Action Third Annual European Symposium on Protein Fractionation and Biomarker Discovery Event date 12.09.2006-13.09.2006 VEvent location Oxford Country GB - United Kingdom Event type WRD Language eng - English Country GB - United Kingdom Keywords cyclin-dependent kinases Subject RIV EB - Genetics ; Molecular Biology R&D Projects GA301/05/0418 GA ČR - Czech Science Foundation (CSF) CEZ AV0Z50450515 - UZFG-Y (2005-2011) AV0Z50200510 - MBU-M (2005-2011) Annotation Cyclin-dependent kinases (CDKs) are key regulators of cell cycle, differentiation and apoptosis. Deregulation of CDKs in many cancer cells has motivated the effort to develop pharmacologically active CDK inhibitors. In this study, we used proteomic approach to monitor response of T-lymphoblastic leukaemia CEM cell line to synthetic CDKs inhibitor, Bohemine. We have compared Bohemine effects on CEM line susceptible to this drug and on a Bohemine resistant cell line derived from CEM line by culture in presence of sub-lethal Bohemine doses. Proteins were separated by two-dimensional liquid chromatography PF 2D system (Beckman Coulter) using chromatofocusing in the first dimension followed by reversed phase HPLC. Changes in protein composition after Bohemine treatment of sensitive and resistant CEM line were evaluated and differently expressed proteins were selected for identification by mass spectrometry. In susceptible cells, down-regulation of three histone variants in response to CDKs inhibition indicated that anti-cancer activity of Bohemine may be associated with epigenetic regulation. Futhermore, down-regulation of Crk-like scaffold adaptor protein was found and verified by immunoblot and immunohistochemistry for in vitro and in vivo drug treatment, respectively. Crk-like protein represents a new important target of CDK inhibition in T-lymphoblastic leukaemia. Response of resistant cells was associated with increase in the level of many chaperones/stress proteins. Workplace Institute of Animal Physiology and Genetics Contact Jana Zásmětová, knihovna@iapg.cas.cz, Tel.: 315 639 554 Year of Publishing 2007
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