About: Wild type and mutant p53 tumor suppressor protein. Intermolecular interactions, changes in conformation and new micro-methods of their analysis     Goto   Sponge   NotDistinct   Permalink

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Description
  • The tumor suppressor protein p53 plays a critical role in the control of cell division and development of cancer. Mutation can result in abolishing the tumor suppressor function of the p53 protein and gain-of-function enhancing the tumorogenicity and metastatic potential. Mutations in the DNA binding domain (DBD) can result in conformational changes of the DBD, which strongly influence the biochemical activities of mutated p53, including DNA binding. Almost nothing is known about the mutant p53 binding to supercoiled (sc) DNA. In this project supercoil-selective and sequence-specific binding of mutant p53 to scDNA will be investigated. In addition new chemical and electrochemical micro-methods of p53 protein analysis and probing of its structure will be developed and used in combination with new %22ProteinChip%22 technology. These methods will be applied to study changes in conformation and interactions of mutated p53 protein in vitro and in cells. (en)
  • Nádorový supresor protein p53 hraje kritickou roli v kontrole buněčného dělení a při vzniku rakoviny. Mutace proteinu p53 může vést ke ztrátě jeho supresorové funkce a naopak k tomu, že podporuje vznik nádorů a jejich metastatický potenciál. Mutace v DNA vazebné doméně (DBD) může vést ke změně konformace proteinu, což silně ovlivňuje biochemické aktivity mutovaného p53, včetně vazby na DNA. Téměř nic není známo o vazbě mutantů p53 na nadšroubovicovou (sc) DNA. V tomto projektu bude zkoumána vazba mutovaného p53 na scDNA s ohledem na její sekvenční specificitu a selektivitu pro nadšroubovicové vinutí. Navíc budou navrženy a rozpracovány nové chemické a elektrochemické mikrometody analysy proteinu p53 a sondy jeho struktury, které budou využity ve spojení s novou technologií %22proteinového čipu%22 (%22ProteinChip%22). Tyto metody budou aplikovány ke studiu konformace a interakcí mutovaného proteinu p53 in vitro a v buňkách.
Title
  • Wild type and mutant p53 tumor suppressor protein. Intermolecular interactions, changes in conformation and new micro-methods of their analysis (en)
  • Standardní (wild type) a mutovaný nádorový supresor protein p53. Mezimolekulární interakce, změny konformace a nové mikrometody jeho analysy
skos:notation
  • IAA500040513
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  • tumor suppressor p53; mutated p53 protein; p53 conformation; electrochemistry of p53; chemical reactivity of p53 (en)
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  • Byly navrženy nové technologie, založené na chemické reaktivitě a elektrochemii proteinu p53 a získány informace o vazbě p53 na superhelikální DNA, podporující EU projekt Mutant p53 as target for improved cancer treatment. (cs)
  • New technologies, based on chemical reactivity and electrochemical behavior of p53 protein, were developed and information about binding of p53 to supercoiled DNA were obtained, supporting the EU project Mutant p53 as target for improved cancer treatment. (en)
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  • tumor suppressor p53
  • electrochemistry of p53
  • mutated p53 protein
  • p53 conformation
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