Transactivation by partial function P53 family mutants is increased by the presence of G-quadruplexes at a promoter site
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F24%3A00600735" target="_blank" >RIV/68081707:_____/24:00600735 - isvavai.cz</a>
Alternative codes found
RIV/00216305:26310/24:PU149826
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0300908423002535?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0300908423002535?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.biochi.2023.09.026" target="_blank" >10.1016/j.biochi.2023.09.026</a>
Alternative languages
Result language
angličtina
Original language name
Transactivation by partial function P53 family mutants is increased by the presence of G-quadruplexes at a promoter site
Original language description
The effect of mutations in the P53 family of transcription factors on their biological functions, including partial or complete loss of transcriptional activity, has been confirmed several times. At present, P53 family proteins showing partial loss of activity appear to be promising potential candidates for the development of novel therapeutic strategies which could restore their transcriptional activity. In this context, it is important to employ tools to precisely monitor their activity, in relation to this, noncanonical DNA secondary structures in promoters including G-quadruplexes (G4s) were shown to influence the activity of transcription factors. Here, we used a defined yeast assay to evaluate the impact of differently modeled G4 forming sequences on a panel of partial function P53 family mutant proteins. Specifically, a 22-mer G4 prone sequence (derived from the KSHV virus) and five derivatives that progressively mutate characteristic guanine stretches were placed upstream of a minimal promoter, adjacent to a P53 response element in otherwise isogenic yeast luciferase reporter strains. The transactivation ability of cancer-associated P53 (TA-P53a: A161T, R213L, N235S, V272L, R282W, R283C, R337C, R337H, and G360V) or Ectodermal Dyplasia syndromes-related P63 mutant proteins (AN-P63a: G134D, G134V and inR155) were tested. Our results show that the presence of G4 forming sequences can increase the transactivation ability of partial function P53 family proteins. These observations are pointing to the importance of DNA structural characteristics for accurate classification of P53 family proteins functionality in the context of the wide variety of TP53 and TP63 germline and somatic mutations. (c) 2023 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA22-21903S" target="_blank" >GA22-21903S: Local DNA structures and their role in mutant p53 protein function in human tumours</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biochimie
ISSN
0300-9084
e-ISSN
1638-6183
Volume of the periodical
216
Issue of the periodical within the volume
JAN 2024
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
10
Pages from-to
14-23
UT code for WoS article
001123328100001
EID of the result in the Scopus database
2-s2.0-85174722006