"0"^^ . "1"^^ . . . . "homologues" . "0"^^ . . . "p53;mutations;chemotherapy;phosphorylation;homologues;activation of p53;CNA damage;tumours"@en . "13"^^ . "mutations" . . "13"^^ . . . . "Anal\u00FDza funk\u010Dn\u00EDch alterac\u00ED mutovan\u00FDch forem proteinu p53 v lidsk\u00FDch n\u00E1dorech." . "2005-07-18+02:00"^^ . "phosphorylation" . "Jedn\u00EDm z prvn\u00EDch c\u00EDl\u016F projektu bude anal\u00FDza efektivnosti \u00FA\u010Dinku alkyla\u010Dn\u00EDch l\u00E1tek, inhibitor\u016F topoizomer\u00E1z, inhibitor\u016F mit\u00F3zy, interkala\u010Dn\u00EDch l\u00E1tek, antimetabolit\u016F a z\u00E1\u0159en\u00ED na n\u00E1dorov\u00E9 bu\u0148ky, exprimuj\u00EDc\u00ED r\u016Fzn\u00E9 mutovan\u00E9 formy proteinu p53. K vyhodnocen\u00ED pod\u00EDlu zapojen\u00ED se fosforylace proteinu p53 v procesu karcinogen\u00E9ze u \u010Dlov\u011Bka, bude provedena obs\u00E1hl\u00E1 studie s vyu\u017Eit\u00EDm spektra lidsk\u00FDch n\u00E1dor\u016F v\u010Detn\u011B molekul\u00E1rn\u00EDch anal\u00FDz statutu vybran\u00FDch fosforylovan\u00FDch m\u00EDst v proteinu p53. Budeme studovat, zda bun\u011B\u010Dn\u00E9 linie exprimuj\u00EDc\u00ED transkrip\u010Dn\u011B aktivn\u00ED mutovanou formu proteinu p53 se mohou pod\u00EDlet na regulaci zv\u00FD\u0161en\u00E9 exprese proteinu CD95/Fas po vyvol\u00E1n\u00ED bun\u011B\u010Dn\u00E9ho strasu a zda zv\u00FD\u0161en\u00E1 exprese koreluje rovn\u011B\u017E s aktivac\u00ED jeho funkce. S vyu\u017Eit\u00EDm dvojit\u00E9 imunohistochemie a na s\u00E9riov\u00FDch \u0159ezech se pokus\u00EDme o v\u00FDvoj metody umo\u017E\u0148uj\u00EDc\u00ED p\u0159edpov\u00EDdat funk\u010Dn\u00ED status proteinu p53 exprimovan\u00E9ho v n\u00E1dorech, koreluj\u00EDc\u00ED s dal\u0161\u00EDmi dostupn\u00FDmi biochemick\u00FDmi metodami." . "CNA damage" . "NC7131" . . . . "Prok\u00E1z\u00E1na d\u016Fle\u017Eitost nemutovan\u00E9 formy proteinu p53 p\u0159i regulaci aktivity konstitutivn\u00ED exprese CD95. Funk\u010Dn\u00ED efekt zv\u00FD\u0161en\u00E9 exprese CD95 po po\u0161kozen\u00ED DNA m\u016F\u017Ee b\u00FDt z\u00E1visl\u00FD na typu bun\u011Bk. Objasn\u011Bna regulace konforma\u010Dn\u00EDch zm\u011Bn p53 vlivem stresov\u00FDch protein\u016F."@cs . "The analysis of effects of alkylating drugs, topoisomerase and mitotic inhibitors, DNA intercalators, antimetabolites and radiation for effectiveness against tumour cells expressing different mutant forms of p53 will be studied. Comprehensive study using a spectrum of excised hu an carcinoma samples including molecular analysis of the status of specific phosphorylation site in p53, will be employet to elucidate the involvement of these phosphorylations in human carcinogenesis. We will examine whether cell lines bearing a transcriptionally active mutant p53 can up-regulete the expression of CD95 after DNA damaging treatments, and whether increased expression correlates with increased function. Using double imunohistochemistry on the routinely used tissue sections we would like to develop the method that will allow us to prdict functional status of p53 protein expressed in tumour that correlates well with the biochemical method."@en . . . "activation of p53" . "chemotherapy" . . "http://www.isvav.cz/projectDetail.do?rowId=NC7131"^^ . "Analysis of functional alterations of mutant forms of p53 protein in human cancers."@en . . "Found wt p53 is important for activity regulation of constitutive expression of CD95, effect of the increased CD95 expression after DNA damage can depend on the cell type and clarified the regulation of conformational changes in p53 by stress proteins."@en . . "p53" . . . .