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Your search keyword '"van Scherpenzeel, Revina C."' showing total 2 results
Start Over Author "van Scherpenzeel, Revina C." Topic wnt signaling pathway
2 results on '"van Scherpenzeel, Revina C."'

1. Axin cancer mutants form nanoaggregates to rewire the Wnt signaling network.

Author

Anvarian Z, Nojima H, van Kappel EC, Madl T, Spit M, Viertler M, Jordens I, Low TY, van Scherpenzeel RC, Kuper I, Richter K, Heck AJ, Boelens R, Vincent JP, Rüdiger SG, and Maurice MM

Subjects
Amino Acid Sequence, Animals, Axin Protein analysis, Axin Protein ultrastructure, Cell Line, Drosophila chemistry, Drosophila genetics, Drosophila metabolism, Drosophila ultrastructure, Drosophila Proteins analysis, Drosophila Proteins genetics, Drosophila Proteins metabolism, HEK293 Cells, Humans, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Missense, Neoplasms metabolism, Neoplasms pathology, Protein Conformation, Protein Interaction Maps, Scattering, Small Angle, Sequence Alignment, X-Ray Diffraction, Axin Protein genetics, Axin Protein metabolism, Neoplasms genetics, Point Mutation, Protein Aggregates, Wnt Signaling Pathway
Abstract

Signaling cascades depend on scaffold proteins that regulate the assembly of multiprotein complexes. Missense mutations in scaffold proteins are frequent in human cancer, but their relevance and mode of action are poorly understood. Here we show that cancer point mutations in the scaffold protein Axin derail Wnt signaling and promote tumor growth in vivo through a gain-of-function mechanism. The effect is conserved for both the human and Drosophila proteins. Mutated Axin forms nonamyloid nanometer-scale aggregates decorated with disordered tentacles, which 'rewire' the Axin interactome. Importantly, the tumor-suppressor activity of both the human and Drosophila Axin cancer mutants is rescued by preventing aggregation of a single nonconserved segment. Our findings establish a new paradigm for misregulation of signaling in cancer and show that targeting aggregation-prone stretches in mutated scaffolds holds attractive potential for cancer treatment.

Published
2016
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2. Axin cancer mutants form nanoaggregates to rewire the Wnt signaling network

Author

Anvarian, Zeinab, Nojima, Hisashi, van Kappel, Eline C, Madl, Tobias, Spit, Maureen, Viertler, Martin, Jordens, Ingrid, Low, Teck Y, van Scherpenzeel, Revina C, Kuper, Ineke, Richter, Klaus, Heck, Albert J R, Boelens, Rolf, Vincent, Jean-Paul, Rüdiger, Stefan G D, Maurice, Madelon M, NMR Spectroscopy, Biomolecular Mass Spectrometry and Proteomics, Cellular Protein Chemistry, Sub NMR Spectroscopy, Sub Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub Cellular Protein Chemistry, NMR Spectroscopy, Biomolecular Mass Spectrometry and Proteomics, Cellular Protein Chemistry, Sub NMR Spectroscopy, Sub Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., and Sub Cellular Protein Chemistry

Subjects
Models, Molecular, 0301 basic medicine, Scaffold protein, Protein Conformation, medicine.disease_cause, Interactome, Mice, X-Ray Diffraction, Structural Biology, Neoplasms, Taverne, Drosophila Proteins, Protein Interaction Maps, Non-U.S. Gov't, Wnt Signaling Pathway, Cancer, Genetics, Mutation, Research Support, Non-U.S. Gov't, Wnt signaling pathway, SAXS, Cell biology, Drosophila, Drosophila Protein, Cell signalling, Cell signaling, Molecular Sequence Data, Mutation, Missense, macromolecular substances, Biology, Research Support, Cell Line, Protein Aggregates, 03 medical and health sciences, Axin Protein, Scattering, Small Angle, medicine, Journal Article, Animals, Humans, Point Mutation, Amino Acid Sequence, Molecular Biology, HEK 293 cells, HEK293 Cells, 030104 developmental biology, Protein–protein interaction networks, Sequence Alignment, Solution-state NMR
Abstract

Signaling cascades depend on scaffold proteins that regulate the assembly of multiprotein complexes. Missense mutations in scaffold proteins are frequent in human cancer, but their relevance and mode of action are poorly understood. Here we show that cancer point mutations in the scaffold protein Axin derail Wnt signaling and promote tumor growth in vivo through a gain-of-function mechanism. The effect is conserved for both the human and Drosophila proteins. Mutated Axin forms nonamyloid nanometer-scale aggregates decorated with disordered tentacles, which 'rewire' the Axin interactome. Importantly, the tumor-suppressor activity of both the human and Drosophila Axin cancer mutants is rescued by preventing aggregation of a single nonconserved segment. Our findings establish a new paradigm for misregulation of signaling in cancer and show that targeting aggregation-prone stretches in mutated scaffolds holds attractive potential for cancer treatment.

Published
2016

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