G-quasruplex structure in proximity of p53 target sequence causes significant inhibition on transactivation potential of p53 isoforms

abstrakt

angličtina

p53 is one of the most studied tumor suppressor proteins that plays an important role in basic biological processes including cell cycle, DNA damage response, apoptosis and senescence. The human TP53 gene contains alternative promoters that produce C-terminally truncated proteins and can produce several isoforms due to alternative splicing. p53 function is realized by binding to a specific DNA response element (RE), resulting in the transactivation of target genes. We evaluated the influence of G-quadruplex structure on the transactivation potential of C-terminal p53 isoforms in a panel of S. cerevisiae luciferase reporter strains. The targeting of p53 RE by the replacement of the ICORE cassette, using transfected single strand oligonucleotides, was performed following the Delitto Perfetto technique. Yeast isogenic strains differing in the p53 target site (with and without cloned G-quadruplex structure) were transformed with plasmid for the expression of p53 isoform proteins. Here we present results of transactivation potential of p53 isoforms and influence of co-expressed isoforms with FLp53 in yeast isogenic system. Our results show that even if p53 binding to G-quadruplex has been shown in the presence of the G-quadruplex-forming sequence, it is not sufficient for p53 transcription activation of all p53 isoforms, moreover the presence of this structure nearby p53 binding site leads to significant decreasing of p53 transcriptional activity.

p53 protein, transactivation potential, G-quadruplex

PORUBIAKOVÁ, O.; BOHÁLOVÁ, N.; BRÁZDA, V.

25. 11. 2020

978-80-214-5920-0

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