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Retroviral insertional mutagenesis implicates E3 ubiquitin ligase RNF168 in the control of cell proliferation and survival

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Aytug Kizilors, Mark R Pickard, Cathleen E Schulte, Kiren Yacqub-Usman, Nicola J McCarthy, Shu-Uin Gan, David Darling, Joop Gäken, Gwyn T Williams, Farzin Farzaneh

Original languageEnglish
Article numberBSR20170843
JournalBioscience Reports
Volume37
Issue number4
Early online date14 Aug 2017
DOIs
Accepted/In press27 Jul 2017
E-pub ahead of print14 Aug 2017
Published31 Aug 2017

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Abstract

The E3 ubiquitin ligase RNF168 is a ring finger protein that has previously been identified to play an important regulatory role in the repair of double-strand DNA breaks. In the present study, an unbiased forward genetics functional screen in mouse granulocyte/ macrophage progenitor cell line FDCP1 has identified E3 ubiquitin ligase RNF168 as a key regulator of cell survival and proliferation. Our data indicate that RNF168 is an important component of the mechanisms controlling cell fate, not only in human and mouse haematopoietic growth factor-dependent cells, but also in the human breast epithelial cell line MCF-7. These observations therefore suggest that RNF168 provides a connection to key pathways controlling cell fate, potentially through interaction with PML nuclear bodies and/or epigenetic control of gene expression. Our study is the first to demonstrate a critical role for RNF168 in the in the mechanisms regulating cell proliferation and survival, in addition to its well-established role in DNA repair.

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