About: Study of the interactions between forkhead transcription factor AFX and DNA.     Goto   Sponge   NotDistinct   Permalink

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Description
  • AFX belongs to FOXO subfamily of Forkhead transcription factors, which are involved in metabolism control, embryogenesis, apoptosis, and tumorigenesis. Activity of these transcription factors is controlled through the phosphorylation by the proteinkinase B and association with 14-3-3 proteins. FOXO transcription factors specifically bind DNA sequence T(G/A)TTTTG, which is known as an insulin response element (IRE). Only small number of structures describing interactions between DNA-binding domainand DNA is available today. Therefore it is impossible to perform detailed structural analysis of interactions between FOXO DNA-binding domain and DNA, and define structural elements responsible for binding specificity. This project suggests to performthis structural analysis using protein crystallography and fluorescence spectroscopy. Such analysis will allow to understand the regulation of DNA-binding specificity as well as overall regulatory mechanism of these important transcription factors. (en)
  • AFX patří do FOXO podrodiny Forkhead transkripčních faktorů, které hrají důležitou roli při kontrole metabolismu, embryogenezi, apoptóze, nebo onkogenezi. Aktivita těchto transkripčních faktorů je regulována fosforylací protein kinázou Ba interakcí se 14-3-3 proteiny. FOXO transkripční faktory specificky váží DNA sekvenci T(G/A)TTTTG, která je známá jako “insulin response element (IRE). V současné době je k dispozici málo strukturních dat popisujících interakce mezi FOXODNA-vazebnou doménou a DNA. To znemožňuje provést strukturní analýzu interakcí FOXO DNA-vazebných domén s DNA a definovat strukturní prvky, které jsou jednoznačně zodpovědné za vazebnou specifitu těchto domén. Tento projekt proto navrhuje provésttuto strukturní analýzu pomocí proteinové krystalografie a fluorescenční spektroskopie. To umožní lépe pochopit mechanismus regulující DNA vazebnou specifitu a vůbec mechanismus celkové regulace těchto biologicky důležitých transkripčních faktorů.
Title
  • Study of the interactions between forkhead transcription factor AFX and DNA. (en)
  • Studium interakcí forkhead transkripčního faktoru AFX s DNA
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  • LZ1K03020
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  • Forkhead transcription factor; AFX; DNA binding; protein crystallography; fluorescence spectroscopy (en)
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  • Vazebné vlastnosti DNA vazebné domény transkripčního faktoru AFX (FoxO4) jsou modulovány konformačními změnami vazebného místa pro DNA v důsledku vazby regulačního 14-3-3 proteinu, který ovlivňuje strukturu různých částí DNA vazebné domény AFX. (cs)
  • Binding properties of DNA binding domain of transcription factor AFX are modulated through conformational changes of the binding site as a consequence of the 14-3-3 protein binding. 14-3-3 changes structure of various parts of DNA binding domain of AFX. (en)
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  • DNA binding
  • protein crystallography
  • AFX
  • Forkhead transcription factor
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