The Mutational Landscape of the Oncogenic MZF1 SCAN Domain in Cancer

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2016 Dec 27

PMID 28018905

Citations 16

Authors

Mads Nygaard

Thilde Terkelsen

Andre Vidas Olsen

Valentina Sora

Juan Salamanca Viloria

Fabio Rizza

Sanne Bergstrand-Poulsen

Miriam Di Marco

Mette Vistesen

Matteo Tiberti

Matteo Lambrughi

Marja Jaattela

Tuula Kallunki

Elena Papaleo

Affiliations

Soon will be listed here.

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.

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