Title | The Mutational Landscape of the Oncogenic MZF1 SCAN Domain in Cancer. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Nygaard M, Terkelsen T, Olsen AVidas, Sora V, Viloria JSalamanca, Rizza F, Bergstrand-Poulsen S, Di Marco M, Vistesen M, Tiberti M, Lambrughi M, Jäättelä M, Kallunki T, Papaleo E |
Journal | Front Mol Biosci |
Volume | 3 |
Pagination | 78 |
Date Published | 2016 |
ISSN | 2296-889X |
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 (), 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. |
DOI | 10.3389/fmolb.2016.00078 |
Alternate Journal | Front Mol Biosci |
PubMed ID | 28018905 |
PubMed Central ID | PMC5156680 |
Grant List | 340751 / / European Research Council / International |