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Quantitative Proteomics Identifies DNA Repair as a Novel Biological Function for Hepatocyte Nuclear Factor 4α in Colorectal Cancer Cells

Department of Anatomy and Cell Biology, Université de Sherbrooke, 3201 Rue Jean-Mignault, Sherbrooke, QC J1E 4K8, Canada
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Cancers 2019, 11(5), 626; https://doi.org/10.3390/cancers11050626
Received: 16 March 2019 / Revised: 2 May 2019 / Accepted: 3 May 2019 / Published: 5 May 2019
(This article belongs to the Special Issue Colorectal Cancers)
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Abstract

Hepatocyte nuclear factor 4α (HNF4α) is a transcription factor that acts as a master regulator of genes for several endoderm-derived tissues, including the intestine, in which it plays a central role during development and tumorigenesis. To better define the mechanisms by which HNF4α can influence these processes, we identified proteins interacting with HNF4α using stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomics with either immunoprecipitation of green fluorescent protein (GFP) or with proximity-dependent purification by the biotin ligase BirA (BioID), both fused to HNF4α. Surprisingly, these analyses identified a significant enrichment of proteins characterized with a role in DNA repair, a so far unidentified biological feature of this transcription factor. Several of these proteins including PARP1, RAD50, and DNA-PKcs were confirmed to interact with HNF4α in colorectal cancer cell lines. Following DNA damage, HNF4α was able to increase cell viability in colorectal cancer cells. Overall, these observations identify a potential role for this transcription factor during the DNA damage response. View Full-Text
Keywords: HNF4α; SILAC; BioID; proteomics; DNA repair; etoposide HNF4α; SILAC; BioID; proteomics; DNA repair; etoposide
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Babeu, J.-P.; Wilson, S.D.; Lambert, É.; Lévesque, D.; Boisvert, F.-M.; Boudreau, F. Quantitative Proteomics Identifies DNA Repair as a Novel Biological Function for Hepatocyte Nuclear Factor 4α in Colorectal Cancer Cells. Cancers 2019, 11, 626.

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