Külalisseminar 30. oktoobril: p53 suppressorvalgu tagasiside ahelate mõistmine
30. oktoobril kell 14.15 toimub Riia 23 ruumis 218 külalisseminar kasvajate suppresorvalgu p53 ja WRAP53 regulatoorse tagasiside mehhanismist ning valgu p53 erinevast fosforüleeritusest tulenevast DNA seondumisvõimest.
Seminaril tutvustab oma teadustöö tulemusi Lõuna-Carolina Ülikooli rakubioloogia professor David Reisman. Ta räägib pikemalt kahest kattuvast projektist: üks neist käsitleb valgu p53 ekspressiooni reguleeriva geeni WRAP53 kontrollimisest, teine aga uuringutest valgu p53 ja DNA seondumise alal.
Pealkiri inglise keeles: „A p53-WRAP53 regulatory feedback loop and implications that phosphorylation of the p53 tumor suppressor protein may cause differential DNA binding“.
p53 is a tumor suppressor gene that is induced in response to DNA damage and is required for cell and genome stability. The p53 mRNA is stabilized through complementary base pairing with the transcript of a gene named WRAP53α; without this interaction, p53 protein fails to accumulate and to carry out its apoptotic or cell cycle related functions. Studies indicate that WRAP53α is induced in response to DNA damage and we identified three putative p53 binding sites on the WRAP53α promoter. Deletion of these sites leads to a loss of WRAP53α induction. We conclude that there may be a positive feedback relationship between WRAP53α and p53, which may be important in mounting a proper DNA damage response.
During the course of these studies, we found that p53 appears to bind differentially to the three binding sites in the WRAP promoter. The regulation of p53 at the post-translational level is important for its DNA damage response, and it is hypothesized that phosphorylation and other post-translational modifications are involved in differential activation of pathways by p53. We have attempted to to identify some locations of phosphorylation on p53 in response to DNA damage with the hope of then examining the impact that specific modifications have on p53’s DNA binding activity. Alternative modifications in response to different modes of DNA damage were observed, and preliminary (very!) evidence indicates that, at some level, these modifications may play a role in p53’s differential DNA binding ability.
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