. . . "regulation; p73; TA73beta; isoform; lung cancer"@en . "1"^^ . "p73 je regulov\u00E1n vn\u011Bj\u0161\u00EDm promotorem (P1) a vnit\u0159n\u00EDm promotorem (P2), je\u017E reguluj\u00ED vznik apoptotick\u00FDch TAp73 a antiapoptotick\u00FDch deltaNp73 izoforem. Z proveden\u00FDch studi\u00ED vypl\u00FDv\u00E1, \u017Ee z\u00E1sadn\u00ED v\u00FDznam p73 v onkogenezi z\u00E1vis\u00ED na pom\u011Bru TA/deltaΝ a \u017Ee odli\u0161n\u00E9 vyu\u017Eit\u00ED promotor\u016F p73 m\u016F\u017Ee zm\u011Bnit tento pom\u011Br apoptotick\u00FDm nebo antiapoptotick\u00FDm sm\u011Brem. Na\u0161e p\u0159edchoz\u00ED studie karcinomu plic uk\u00E1zaly, \u017Ee promotor P1 je p\u0159ev\u00E1\u017En\u011B nemetylovan\u00FD a je upregulov\u00E1n faktorem Sp1, zat\u00EDmco hypometylace promotoru P2 je p\u0159\u00ED\u010Dinou overexprese deltaN. Tak\u00E9 jsme zjistili, \u017Ee TAp73gama je jedinou izoformou exprimovanou v bu\u0148k\u00E1ch plicn\u00EDho karcinomu, a je tedy ot\u00E1zkou, jak\u00FD je apoptotick\u00FD efekt t\u00E9to izoformy. Na z\u00E1klad\u011B uveden\u00FDch zji\u0161t\u011Bn\u00ED si klademe za c\u00EDl: a) identifikovat transkrip\u010Dn\u00ED faktory reguluj\u00EDc\u00ED P2,b) studovat roli nej\u00FA\u010Dinn\u011Bj\u0161\u00ED apoptotick\u00E9 TA izoformy TΑp73beta ve srovn\u00E1n\u00ED s izoformou TAp73gama u karcinomu plic s vyu\u017Eit\u00EDm specifick\u00FDch protil\u00E1tek proti jednotliv\u00FDm p73 izoform\u00E1m, kter\u00E9 budou vytvo\u0159eny na na\u0161em pracovi\u0161ti."@cs . . "0"^^ . . "0"^^ . "p73 possesses an extrinsic promoter (P1) an intrinsic promoter (P2), synthesizing apoptotic TAp73 and antiapoptotic deltaΝp73 classes of isoforms, respectively. Studies suggest that the ultimate effect of p73 in oncogenesis depends on TA/deltaΝ ratio and that the control of p73 promoters\u2019 usage could shift this ratio towards an apoptotic or an antiapoptotic direction. Our previous studies in lung cancer showed that P1 is mainly unmethylated and upregulated by Sp1 transcription factor, whereas P2 hypomethylation accounts for deltaΝ overexpression. We also found that TAp73gamma is the only isoform expressed in lung cancer cell, thus questioning the apoptotic efficiency of this specific isoform. In light of the above evidence, we aim to a) identify transcription factors of P2 and, b) study the role of the most potent apoptotic TA isoform, ie TΑp73beta, in comparison with TAp73gamma, in lung cancer, using high-resolution, isoform-specific p73 antibodies that will be produced in-house."@en . "2012-01-01+01:00"^^ . "0"^^ . . "50"^^ . . "50"^^ . . "Regulace genu p73 a role izoformy TA73beta u karcinomu plic."@cs . "2013-12-31+01:00"^^ . "The regulation of p73 gene and the role of TA73beta isoform in lung cancer"@en . . . . "0"^^ .