the mutational landscape of the oncogenic mzf1 scan domain in cancer
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ID: 221705
2016
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Abstract
SCAN domains in zinc-finger transcription factors are crucial mediators of protein-protein interactions. Up to 240 SCAN-domain encoding genes have been identified throughout the human genome. These include cancer-related genes, such as the myeloid zinc finger 1 (MZF1), an oncogenic transcription factor involved in the progression of many solid cancers. The mechanisms by which SCAN homo- and heterodimers assemble and how they alter the transcriptional activity of zinc-finger transcription factors in cancer and other diseases remain to be investigated. Here, we provide the first description of the conformational ensemble of the MZF1 SCAN domain cross-validated against NMR experimental data, which are probes of structure and dynamics on different timescales. We investigated the protein-protein interaction network of MZF1 and how it is perturbed in different cancer types by the analyses of high-throughput proteomics and RNASeq data. Collectively, we integrated many computational approaches, ranging from simple empirical energy functions to all-atom microsecond molecular dynamics simulations and network analyses to unravel the effects of cancer-related substitutions in relation to MZF1 structure and interactions.
| Reference Key |
nygaard2016frontiersthe
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| Authors | ;Mads Nygaard;Thilde Terkelsen;Andre Vidas Olsen;Valentina Sora;Juan Salamanca Viloria;Fabio Rizza;Sanne Bergstrand;Miriam Di Marco;Mette Vistesen;Matteo Tiberti;Matteo Lambrughi;Marja Jaattela;Tuula Kallunki;Elena Papaleo |
| Journal | biopsychosocial medicine |
| Year | 2016 |
| DOI |
10.3389/fmolb.2016.00078
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| URL | |
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