PI3Kδ activates E2F1 synthesis in response to mRNA translation stress

Sivakumar Vadivel Gnanasundram, Slovénie Pyndiah, Chrysoula Daskalogianni, Kate Armfield, Karin Nylander, Joanna B. Wilson and Robin Fåhraeus ()
Additional contact information
Sivakumar Vadivel Gnanasundram: Hôpital St. Louis
Slovénie Pyndiah: Hôpital St. Louis
Chrysoula Daskalogianni: Hôpital St. Louis
Kate Armfield: University of Glasgow
Karin Nylander: Umeå University
Joanna B. Wilson: University of Glasgow
Robin Fåhraeus: Hôpital St. Louis

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract 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.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02282-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02282-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-02282-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().