"http://www.isvav.cz/projectDetail.do?rowId=GA204/08/1530"^^ . "We have shown that knockout of the HMGB1 gene (HMGB1-/-) resulted in immortalized mouse embryonic fibroblasts (MEFs) in significant (>5-fold) decrease in telomerase activity. Correspondingly, enhanced telomerase activity was detected in MEFs with (plasmid-directed) over-expression of HMGB1 protein.  MEFs lacking HMGB1 protein exhibited striking chromosomal abnormalities, a moderate shorte"@en . . " p53" . "GA204/08/1530" . . . . . . "Poda\u0159ilo se n\u00E1m prok\u00E1zat, \u017Ee knockout HMGB1 genu v imortalizovan\u00FDch my\u0161\u0161\u00EDch embryon\u00E1ln\u00EDch fibroblastech (MEF) vede k signifikantn\u00EDmu poklesu (>5-kr\u00E1t) telomer\u00E1zov\u00E9 aktivity.V souladu s timto n\u00E1lezem jsme prok\u00E1zali zv\u00FD\u0161enou telomer\u00E1zovou aktivitu v MEF bu\u0148k\u00E1ch exprimuj\u00EDc\u00EDch protein HMGB1 (k\u00F3dovan\u00FD plazmidem). MEF bu\u0148ky postr\u00E1daj\u00EDc\u00ED HMGB1 vykazuj\u00ED zna\u010Dn\u00E9 chromozom\u00E1ln\u00ED abnormality a zkr\u00E1cen\u00ED d\u00E9le"@cs . "Understanding of HMGB1 protein involvement in maintaining genome stability"@en . "2008-01-01+01:00"^^ . "13"^^ . "13"^^ . . "2010-12-31+01:00"^^ . . . "1"^^ . "HMGB1 je protein asociovan\u00FD s chromatinem a ned\u00E1vn\u00E9 n\u00E1lezy prok\u00E1zaly souvislost mezi delec\u00ED HMGB1 genu a extr\u00E9mn\u00ED chromoz\u00F3movou nestabilitou pozorovanou u my\u0161\u00EDch fibroblast\u016F. Jeden z mechanism\u016F objas\u0148uj\u00EDc\u00EDch chromoz\u00F3movou nestabilitu zahrnuje poruchu funkce telomer, specifick\u00FDch nukleoproteinov\u00FDch struktur chr\u00E1n\u00EDc\u00EDch konce chromoz\u00F3m\u016F p\u0159ed rekombinac\u00ED a degradac\u00ED. Ned\u00E1vno jsme objevili, \u017Ee inaktivace HMGB1 genu vede u my\u0161\u00EDch bun\u011Bk k poklesu aktivity telomer\u00E1zy (prodlu\u017Euje telomery), zkr\u00E1cen\u00ED nebo ztr\u00E1tu telomer, a v ojedin\u011Bl\u00FDch p\u0159\u00EDpadech i jejich prodlou\u017Een\u00ED (nez\u00E1visl\u00E9 na telomer\u00E1ze). Poda\u0159ilo se n\u00E1m rovn\u011B\u017E identifikovat HMGB1 jako protein v\u00E1\u017E\u00EDc\u00ED se s telomer\u00E1zou in vitro. Jeliko\u017E exprese HMGB1 je vysok\u00E1 u v\u011Bt\u0161iny n\u00E1dor\u016F, lze se domn\u00EDvat, \u017Ee jej\u00EDderegulace m\u016F\u017Ee m\u00EDt katastrof\u00E1ln\u00ED d\u016Fsledky i pro strukturu telomer. V p\u0159edkl\u00E1dan\u00E9m projektu budeme sledovat vliv exprese HMGB1 (sn\u00ED\u017Een\u00ED nebo zv\u00FD\u0161en\u00ED) v lidsk\u00FDch bu\u0148k\u00E1ch s definovan\u00FDm statutem p53 na: (i) aktivitu telomer\u00E1zy, (ii) expresi proteinov\u00E9" . "1"^^ . "HMGB1" . . . "0"^^ . . . . " transactivation of genes" . . "Objasn\u011Bn\u00ED \u00FAlohy proteinu HMGB1 v udr\u017Eov\u00E1n\u00ED genomov\u00E9 stability" . . " genomic integrity" . "HMGB1 is a relatively abundant chromatin-associated protein and recent data indicated striking chromosomal instability in HMGB1 knock-outed primary mouse embryonic fibroblasts. One mechanism for chromosome instability is through the dysfunction of telomeres, the specific nucleoprotein structures forming chromosome ends and protecting them from recombination and degradation. Recently we have discovered that deficiency of HMGB1 in mouse cells resulted in lower telomerase activity, general telomere shortening or loss, and occasional telomere expansions. We have also identified HMGB1 as a telomerase-associated protein in vitro. As most, if not all, tumor cells over-express HMGB1, deregulated expression of HMGB1 could have catastrophic consequences for the structure of telomeres. In this project we intend to study the impact of aberrant HMGB1 expression (silencing or over-expression) in human cells with different status of tumor suppressor protein p53 on: (i) the activity of telomerase; (ii) the"@en . "2015-02-09+01:00"^^ . . . . "HMGB1; p53; transactivation of genes; genomic integrity; telomeres"@en . . "2010-04-16+02:00"^^ .