Translational control of E2f1 regulates the Drosophila cell cycle

Author:

Øvrebø Jan Inge1ORCID,Bradley-Gill Mary-Rose2ORCID,Zielke Norman3,Kim Minhee2,Marchetti Marco1,Bohlen Jonathan4ORCID,Lewis Megan1ORCID,van Straaten Monique4ORCID,Moon Nam-Sung2,Edgar Bruce A.1ORCID

Affiliation:

1. Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112

2. McGill University, Montreal, QC H3A 0G4, Canada

3. University of Helsinki, 00014 Helsinki, Finland

4. Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany

Abstract

Significance Here, we explore a mechanism wherein the growth signaling-dependent translation of mRNA encoding a cell cycle regulatory factor limits rates of cell proliferation. An essential cell cycle transcription factor, E2F1, was found to be post-transcriptionally regulated by TOR and EGFR signaling, and thus served as a candidate growth sensor for this study. Using expression of green fluorescent protein (GFP)-E2F1 transgenes with alterations within the E2f1 5′ untranslated region (UTR), we altered the translation of GFP-E2F1 and changed cell proliferation rates accordingly. Further, we found that 5′UTR upstream open reading frames are TOR-sensitive regulatory components of E2f1 translation. Our observations indicate that growth signaling dependent protein translation is an important regulator of cell proliferation.

Funder

HHS | NIH | National Institute of General Medical Sciences

EC | FP7 | FP7 Ideas: European Research Council

Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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