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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2021

AutorInnen: Terlecki-Zaniewicz, S; Humer, T; Eder, T; Schmoellerl, J; Heyes, E; Manhart, G; Kuchynka, N; Parapatics, K; Liberante, FG; Müller, AC; Tomazou, EM; Grebien, F

Titel: Biomolecular condensation of NUP98 fusion proteins drives leukemogenic gene expression.

Quelle: Nat Struct Mol Biol. 2021 28 (2) 190-+.


Entstanden unter Nutzung der Ressourcen von
VetCore (VetImaging);

Autor/innen der Vetmeduni Vienna:

Eder Thomas
Grebien Florian
Heyes Elizabeth Claire
Manhart Gabriele
Schmöllerl Johannes

Beteiligte Vetmed-Organisationseinheiten
Institut für Medizinische Biochemie


Zugehörige(s) Projekt(e): Common Oncogenic Mechanisms in Multi-Partner Translocation Families in Acute Myeloid Leukemia


Abstract:
NUP98 fusion proteins cause leukemia via unknown molecular mechanisms. All NUP98 fusion proteins share an intrinsically disordered region (IDR) in the NUP98 N terminus, featuring repeats of phenylalanine-glycine (FG), and C-terminal fusion partners often function in gene control. We investigated whether mechanisms of oncogenic transformation by NUP98 fusion proteins are hardwired in their protein interactomes. Affinity purification coupled to mass spectrometry (MS) and confocal imaging of five NUP98 fusion proteins expressed in human leukemia cells revealed that shared interactors were enriched for proteins involved in biomolecular condensation and that they colocalized with NUP98 fusion proteins in nuclear puncta. We developed biotinylated isoxazole-mediated condensome MS (biCon-MS) to show that NUP98 fusion proteins alter the global composition of biomolecular condensates. An artificial FG-repeat-containing fusion protein phenocopied the nuclear localization patterns of NUP98 fusion proteins and their capability to drive oncogenic gene expression programs. Thus, we propose that IDR-containing fusion proteins combine biomolecular condensation with transcriptional control to induce cancer.

Keywords Pubmed: Animals
Cell Nucleusmetabolism
Gene Expression
Gene Expression Regulation, Leukemic
HEK293 Cells
HL-60 Cells
Homeodomain Proteinschemistryphysiology
Humans
Leukemiametabolismpathology
Mice
NIH 3T3 Cells
Nuclear Pore Complex Proteinschemistryphysiology
Oncogene Proteins, Fusionchemistryphysiology

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