Publication detail

Attenuation of p53-alpha isoform transactivation by inverted repeat sequences in p53 target sites

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

1

Pages count

1

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"
}