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PORUBIAKOVÁ, O. BOHÁLOVÁ, N. INGA, A. BRÁZDA, V.
Original Title
Attenuation of p53-alpha isoform transactivation by inverted repeat sequences in p53 target sites
Type
abstract
Language
English
Original Abstract
p53 is one of the most studied tumour suppressor proteins, playing important roles in regulating basic biological processes including cell cycle, apoptosis, senescenceand metabolism. The human Tp53 gene contains alternative promoters and thanks to alternative splicing can produce several isoforms. p53 protein function is realizedby binding to specific DNA response elements resulting in the transactivation of target genes. Here we present results of p53alpha isoform obtained using a yeastisogenic system for in vivo transactivation studies in chromosomal context to specifically evaluate the influence of secondary DNA structures on transactivation. We useda panel of S. cerevisiaehaploid strains that are isogenic except for different p53 DNA binding sites positioned upstream of a luciferase reporter gene and chosen basedon different propensities to form DNA structures. The targeting of the chosen p53 binding site was achieved by the Delitto Perfettooligonucleotide targeting techniqueby the replacement of a double reporter ICORE cassette, facilitated by the induction of a single sitespecific DNA double strand break. The obtained yeast reporterstrains differing in the p53 target site (with and without propensity to form cruciform structure) were transformed with a plasmid for the expression of p53alpha. Ourresults show that transactivation is correlated better with the relative propensity of a response element to form cruciform structure than to its predicted DNA bindingaffinity. These results point to the fact that structural features of DNAs are an important determinant to its DNAbinding and transactivation function. In the followupexperiments we would compare DNAbinding and transactivation potential of other p53 isoforms relevant in cancer development, expressed alone or coexpressedwith p53alpha.
Keywords
p53; transactivation;
Authors
PORUBIAKOVÁ, O.; BOHÁLOVÁ, N.; INGA, A.; BRÁZDA, V.
Released
1. 7. 2019
ISBN
2211-5463
Periodical
FEBS Open Bio
Year of study
9
Number
S1
State
United Kingdom of Great Britain and Northern Ireland
Pages from
1
Pages to
Pages count
URL
https://2019.febscongress.org/abstract_preview.aspx?idAbstractEnc=4424170094096098094092424170
BibTex
@misc{BUT163525, author="PORUBIAKOVÁ, O. and BOHÁLOVÁ, N. and INGA, A. and BRÁZDA, V.", title="Attenuation of p53-alpha isoform transactivation by inverted repeat sequences in p53 target sites", year="2019", journal="FEBS Open Bio", volume="9", number="S1", pages="1--1", issn="2211-5463", url="https://2019.febscongress.org/abstract_preview.aspx?idAbstractEnc=4424170094096098094092424170", note="abstract" }