The foggy world(s) of p63 isoform regulation in normal cells and cancer
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F21%3A00078561" target="_blank" >RIV/00209805:_____/21:00078561 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/21:00123632
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/10.1002/path.5656" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/path.5656</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/path.5656" target="_blank" >10.1002/path.5656</a>
Alternative languages
Result language
angličtina
Original language name
The foggy world(s) of p63 isoform regulation in normal cells and cancer
Original language description
The p53-family member, p63, exists as two major protein variants (TAp63 and ΔNp63) with distinct expression patterns and functional properties. Whilst downstream target genes of p63 have been studied intensively, how p63 variants are themselves controlled has been relatively neglected. Here, we review advances in understanding ΔNp63 and TAp63 regulation, highlighting their distinct pathways. TAp63 has roles in senescence and metabolism, and in germ cell genome maintenance, where it is activated post-transcriptionally by phosphorylation cascades after DNA damage. The function and regulation of TAp63 in mesenchymal and haematopoietic cells is less clear but may involve epigenetic control through DNA methylation. ΔNp63 functions to maintain stem/progenitor cells in various epithelia and is overexpressed in squamous and certain other cancers. ΔNp63 is transcriptionally regulated through multiple enhancers in concert with chromatin modifying proteins. Many signalling pathways including growth factors, morphogens, inflammation and the extracellular matrix influence ΔNp63 levels, with inconsistent results reported. There is also evidence for reciprocal regulation, including ΔNp63 activating its own transcription. ΔNp63 is downregulated during cell differentiation through transcriptional regulation, while post-transcriptional events cause proteasomal degradation. Throughout the review, we identify knowledge gaps and highlight discordances, providing potential explanations including cell-context and cell-matrix interactions. Identifying individual p63 variants has roles in differential diagnosis and prognosis, and understanding their regulation suggests clinically approved agents for targeting p63 that may be useful combination therapies for selected cancer patients.
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
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of pathology
ISSN
0022-3417
e-ISSN
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Volume of the periodical
254
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
20
Pages from-to
454-473
UT code for WoS article
000637618600001
EID of the result in the Scopus database
2-s2.0-85104018560