Distinct p53 phosphorylation patterns in chronic lymphocytic leukemia patients are reflected in the activation of circumjacent pathways upon DNA damage
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F23%3A00077931" target="_blank" >RIV/65269705:_____/23:00077931 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14740/23:00130102
Result on the web
<a href="https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1878-0261.13337" target="_blank" >https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1878-0261.13337</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/1878-0261.13337" target="_blank" >10.1002/1878-0261.13337</a>
Alternative languages
Result language
angličtina
Original language name
Distinct p53 phosphorylation patterns in chronic lymphocytic leukemia patients are reflected in the activation of circumjacent pathways upon DNA damage
Original language description
TP53 gene abnormalities represent the most important biomarker in chronic lymphocytic leukemia (CLL). Altered protein modifications could also influence p53 function, even in the wild-type protein. We assessed the impact of p53 protein phosphorylations on p53 functions as an alternative inactivation mechanism. We studied p53 phospho-profiles induced by DNA-damaging agents (fludarabine, doxorubicin) in 71 TP53-intact primary CLL samples. Doxorubicin induced two distinct phospho-profiles: profile I (heavily phosphorylated) and profile II (hypophosphorylated). Profile II samples were less capable of activating p53 target genes upon doxorubicin exposure, resembling TP53-mutant samples at the transcriptomic level, whereas standard p53 signaling was triggered in profile I. ATM locus defects were more common in profile II. The samples also differed in the basal activity of the hypoxia pathway: the highest level was detected in TP53-mutant samples, followed by profile II and profile I. Our study suggests that wild-type TP53 CLL cells with less phosphorylated p53 show TP53-mutant-like behavior after DNA damage. p53 hypophosphorylation and the related lower ability to respond to DNA damage are linked to ATM locus defects and the higher basal activity of the hypoxia pathway.
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
30204 - Oncology
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)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Oncology
ISSN
1574-7891
e-ISSN
1878-0261
Volume of the periodical
17
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
16
Pages from-to
82-97
UT code for WoS article
000917264200005
EID of the result in the Scopus database
2-s2.0-85143503676