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Disclosing the Interactome of Leukemogenic NUP98-HOXA9 and SET-NUP214 Fusion Proteins Using a Proteomic Approach

1
Institute of Molecular Biology and Medicine, Université Libre de Bruxelles, 6041 Charleroi, Belgium
2
Present address: Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, 52074 Aachen, Germany
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(7), 1666; https://doi.org/10.3390/cells9071666
Received: 2 June 2020 / Revised: 7 July 2020 / Accepted: 7 July 2020 / Published: 10 July 2020
(This article belongs to the Section Cell Nuclei: Function, Transport and Receptors)
The interaction of oncogenes with cellular proteins is a major determinant of cellular transformation. The NUP98-HOXA9 and SET-NUP214 chimeras result from recurrent chromosomal translocations in acute leukemia. Functionally, the two fusion proteins inhibit nuclear export and interact with epigenetic regulators. The full interactome of NUP98-HOXA9 and SET-NUP214 is currently unknown. We used proximity-dependent biotin identification (BioID) to study the landscape of the NUP98-HOXA9 and SET-NUP214 environments. Our results suggest that both fusion proteins interact with major regulators of RNA processing, with translation-associated proteins, and that both chimeras perturb the transcriptional program of the tumor suppressor p53. Other cellular processes appear to be distinctively affected by the particular fusion protein. NUP98-HOXA9 likely perturbs Wnt, MAPK, and estrogen receptor (ER) signaling pathways, as well as the cytoskeleton, the latter likely due to its interaction with the nuclear export receptor CRM1. Conversely, mitochondrial proteins and metabolic regulators are significantly overrepresented in the SET-NUP214 proximal interactome. Our study provides new clues on the mechanistic actions of nucleoporin fusion proteins and might be of particular relevance in the search for new druggable targets for the treatment of nucleoporin-related leukemia. View Full-Text
Keywords: SET-NUP214; NUP98-HOXA9; BioID; interactome; gene ontology; leukemia SET-NUP214; NUP98-HOXA9; BioID; interactome; gene ontology; leukemia
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Mendes, A.; Jühlen, R.; Bousbata, S.; Fahrenkrog, B. Disclosing the Interactome of Leukemogenic NUP98-HOXA9 and SET-NUP214 Fusion Proteins Using a Proteomic Approach. Cells 2020, 9, 1666.

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