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

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


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.

Acceptance Date Jul 27, 2017
Publication Date Jul 27, 2017
Publicly Available Date Mar 28, 2024
Journal Bioscience Reports
Print ISSN 0144-8463
Publisher Portland Press
DOI https://doi.org/10.1042/BSR20170843
Keywords Retroviral Insertional Mutagenesis, Ubiquitin, apoptosis, cell proliferation, cell survival
Publisher URL http://dx.doi.org/10.1042/BSR20170843

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