Post date: Nov 18, 2016 2:16:55 PM
The mutational landscape of the oncogenic MZF1 SCAN domain in cancer
Mads Nygaard(1) , Thilde Terkelsen(1), 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*
(1) equally contributing authors
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.
in press on Frontiers in Mol Biosci
http://journal.frontiersin.org/article/10.3389/fmolb.2016.00078/abstract