. . . . "2015-12-31+01:00"^^ . "1"^^ . . "V\u00FDvoj n\u00E1doru je mnohastup\u0148ov\u00FD proces zahrnuj\u00EDc\u00ED aktivaci onkogen\u016F a inaktivaci n\u00E1dorov\u00FDch supresor\u016F pomoc\u00ED mutac\u00ED nebo epigenetick\u00FDch faktor\u016F (zm\u011Bn). Ned\u00E1vno publikovan\u00E1 data ukazuj\u00ED, \u017Ee n\u00E1dorov\u00E9 bu\u0148ky vykazuj\u00ED tak\u00E9 abnorm\u00E1ln\u00ED aktivitu chaperon\u016F, kter\u00E9 zaji\u0161\u0165uj\u00ED spr\u00E1vn\u00E9 skl\u00E1d\u00E1n\u00ED protein\u016F. Tyto abnormality podporuj\u00ED schopnosti inhibitor\u016F Hsp90 c\u00EDlen\u011B p\u016Fsobit na n\u00E1dorov\u00E9 bu\u0148ky s minin\u00E1ln\u00EDm efektem na bu\u0148ky norm\u00E1ln\u00ED. V ned\u00E1vn\u00E9 dob\u011B jsme prok\u00E1zali, \u017Ee mutantn\u00ED n\u00E1dorov\u00FD supresor protein p53 je regulov\u00E1n syst\u00E9mem Hsp70/Hsp90 v kombinaci s ko-chaperony, kter\u00E9 vedou bu\u010F k jeho stabilizaci nebo degradaci. Role ko-chaperon\u016F p\u0159i rozhodov\u00E1n\u00ED, zda bude protein skl\u00E1d\u00E1n nebo degradov\u00E1n, z\u016Fst\u00E1v\u00E1 nejasn\u00E1, poskytuje v\u0161ak nov\u00FD p\u0159\u00EDstup pro navrhov\u00E1n\u00ED l\u00E9\u010Div. Budeme studovat roli chaperonov\u00E9ho/ko-chaperonov\u00E9ho syst\u00E9mu u n\u00E1dorov\u00FDch onemocn\u011Bn\u00ED a identifikovat mechanismy \u00FA\u010Dastn\u00EDc\u00ED se hyperaktivace tohoto syst\u00E9mu v n\u00E1dorov\u00FDch bu\u0148k\u00E1ch. D\u00E1le se budeme zab\u00FDvat vlivem ko-chaperon\u016F a celkov\u00FDm efektem na expresi a aktivitu klientsk\u00FDch protein\u016F s onkogenn\u00ED funkc\u00ED." . "0"^^ . "2011-01-01+01:00"^^ . "cancer chaperon co-chaperon Hsp90 p53 protein conformation"@en . "http://www.isvav.cz/projectDetail.do?rowId=GAP301/11/1678"^^ . . "2015-04-23+02:00"^^ . "0"^^ . . "2014-03-31+02:00"^^ . . . "The role of the chaperone system in malignant transformation and response to anti-cancer therapy"@en . . "\u00DAloha chaperonov\u00E9ho syst\u00E9mu v malign\u00ED transformaci a odpov\u011Bdi na protin\u00E1dorovou terapii" . "GAP301/11/1678" . . . . . . "9"^^ . . . "9"^^ . . "Tumour development is a multi-step process that involves activation of oncogenes and inactivation of tumour suppressor genes by genetic mutations and epigenetic alterations. Recent data have indicated that cancer cells have abnormal activities of chaperones that act to ensure correct folding of proteins. These abnormalities underpin the ability of Hsp90 inhibitors to effectively target cancer cells with minimal effects on normal cells. We have recently demonstrated that mutant p53 tumour suppressor protein is regulated by the Hsp70/Hsp90 system in combination with co-chaperones, leading either to stabilization or degradation. The role of co-chaperones in deciding whether a protein is targeted for folding or degradation is unclear, but provides a novel approach to design therapeutic agents. We will investigate the role of the chaperone/co-chaperone system in cancer by identifying the mechanisms involved in hyper-activation in cancer cells, the modifying effects of co-chaperones and the overall effect on the expression and activity of client proteins with oncogenic roles."@en . .