Detail publikace

Effect of G-Quadruplex Structures on the Transcription Activity of Oncologically Important Proteins

KRATOCHVILOVÁ, L. INGA, A. MONTI, P. BRÁZDA, V.

Originální název

Typ

abstrakt

Jazyk

angličtina

Originální abstrakt

G-quadruplexes (G4s) are secondary quaternary local structures of DNA or RNA that are essential for fundamental biological processes. Presence of G4s in key genomic regions, such as oncogene promoters, highlights their potential as targets for novel anticancer therapies (1). Currently, research is focused on elucidating the interactions of G4s with oncologically relevant proteins such as, among others, one of the most mutated proteins, p53, which acts as a guardian of the genome (2). In this study, the effect of G4 structures on the modulation of gene expression induced by p53 or NF-kB family proteins in the yeast one-hybrid expression system (Y1H), was investigated. The isogenic Saccharomyces cerevisiae yLFM strains containing the sequences derived from human gene promoters containing responsive elements (REs) and native G4 structures or REs with CT-control sequence were used. The activity of the p53 or NF-kB proteins was monitored under an inducible promoter to obtain moderate or high levels of protein expression. The results observed in Y1H demonstrated that G4 structures significantly enhance basal gene transcription, irrespective of their downstream or upstream position relative to REs or presence of spacer or overlap of the REs-G4s sequences. Analysis of the transcriptional activity of p53 protein family members showed an increase in the activity of all proteins in G4-containing strains. The increase in activity was more significant for weaker TFs and inversely proportional to the protein activity observed in control strains. The effect of G4 modulation of gene expression was also observed in strains carrying REs of NF-kB family proteins, where G4 was located on the negative strand. These findings underscore the modulatory role of G4s in transcriptional regulation, offering new insights into their mutual interactions with important human transcription factors, and highlighting their potential as therapeutic targets.

Klíčová slova

G-quadruplex, p53 proteins, NF-kB proteins, yeast one-hybrid isogenic system

Autoři

KRATOCHVILOVÁ, L.; INGA, A.; MONTI, P.; BRÁZDA, V.

Vydáno

13. 5. 2025

ISSN

1336-4839

Periodikum

34th Annual Conference on Yeasts, Book of abstracts

Stát

Slovenská republika

Strany od

Strany do

Strany počet

BibTex

@misc{BUT198010,
  author="KRATOCHVILOVÁ, L. and INGA, A. and MONTI, P. and BRÁZDA, V.",
  title="Effect of G-Quadruplex Structures on the Transcription Activity of Oncologically 
Important Proteins",
  year="2025",
  journal="34th Annual Conference on Yeasts, Book of abstracts",
  pages="64--64",
  issn="1336-4839",
  note="abstract"
}