PI3Kδ activates E2F1 synthesis in response to mRNA translation stress
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F17%3A00077848" target="_blank" >RIV/00209805:_____/17:00077848 - isvavai.cz</a>
Result on the web
<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29235459/" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29235459/</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-017-02282-w" target="_blank" >10.1038/s41467-017-02282-w</a>
Alternative languages
Result language
angličtina
Original language name
PI3Kδ activates E2F1 synthesis in response to mRNA translation stress
Original language description
The c-myc oncogene stimulates ribosomal biogenesis and protein synthesis to promote cellular growth. However, the pathway by which cells sense and restore dysfunctional mRNA translation and how this is linked to cell proliferation and growth is not known. We here show that mRNA translation stress in cis triggered by the gly-ala repeat sequence of Epstein-Barr virus (EBV)-encoded EBNA1, results in PI3Kδ-dependent induction of E2F1 mRNA translation with the consequent activation of c-Myc and cell proliferation. Treatment with a specific PI3Kδ inhibitor Idelalisib (CAL-101) suppresses E2F1 and c-Myc levels and causes cell death in EBNA1-induced B cell lymphomas. Suppression of PI3Kδ prevents E2F1 activation also in non-EBV-infected cells. These data illustrate an mRNA translation stress-response pathway for E2F1 activation that is exploited by EBV to promote cell growth and proliferation, offering new strategies to treat EBV-carrying cancers.
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
10601 - Cell 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
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature communications
ISSN
2041-1723
e-ISSN
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Volume of the periodical
8
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
10
Pages from-to
2103
UT code for WoS article
000417884500009
EID of the result in the Scopus database
2-s2.0-85038398654