AUTHOR=Nygaard Mads , Terkelsen Thilde , Vidas Olsen André , Sora Valentina , Salamanca Viloria Juan , Rizza Fabio , Bergstrand-Poulsen Sanne , Di Marco Miriam , Vistesen Mette , Tiberti Matteo , Lambrughi Matteo , Jäättelä Marja , Kallunki Tuula , Papaleo Elena TITLE=The Mutational Landscape of the Oncogenic MZF1 SCAN Domain in Cancer JOURNAL=Frontiers in Molecular Biosciences VOLUME=3 YEAR=2016 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2016.00078 DOI=10.3389/fmolb.2016.00078 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 (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.