Computational analysis of the evolutionarily conserved Missing In Metastasis/Metastasis Suppressor 1 gene predicts novel interactions, regulatory regions and transcriptional control
| Autor: | Petar Petrov, Alexey V. Sarapulov, Lel Eöry, Cristina Scielzo, Lydia Scarfò, Jacqueline Smith, David W. Burt, Pieta K. Mattila |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Polymorphism Genetic lcsh:R Microfilament Proteins lcsh:Medicine Lizards Regulatory Sequences Nucleic Acid Article Leukemia Lymphoid Neoplasm Proteins Evolution Molecular Protein Domains otorhinolaryngologic diseases Animals Humans lcsh:Q lcsh:Science Chickens Conserved Sequence Protein Binding |
| Zdroj: | Petrov, P, Sarapulov, A V, Eory, L, Scielzo, C, Scarfo, L, Smith, J, Burt, D W & Mattila, P K 2019, ' Computational analysis of the evolutionarily conserved Missing In Metastasis/Metastasis Suppressor 1 gene predicts novel interactions, regulatory regions and transcriptional control ', Scientific Reports . https://doi.org/10.1038/s41598-019-40697-1 Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-17 (2019) |
| DOI: | 10.1038/s41598-019-40697-1 |
| Popis: | Missing in Metastasis (MIM), or Metastasis Suppressor 1 (MTSS1), is a highly conserved protein, which links the plasma membrane to the actin cytoskeleton. MIM has been implicated in various cancers, however, its modes of action remain largely enigmatic. Here, we performed an extensive in silico characterisation of MIM to gain better understanding of its function. We detected previouslyunappreciated functional motifs including adaptor protein (AP) complex interaction site and a C-helix, pointing to a role in endocytosis and regulation of actin dynamics, respectively. We also identified new functional regions, characterised with phosphorylation sites or distinct hydrophilic properties.Strong negative selection during evolution, yielding high conservation of MIM, has been combined with positive selection at key sites. Interestingly, our analysis of intra-molecular co-evolution revealed potential regulatory hotspots that coincided with reduced potentially pathogenic polymorphisms. We explored databases for the mutations and expression levels of MIM in cancer. Experimentally, we focused on chronic lymphocytic leukaemia (CLL), where MIM showed high overall expression, however, downregulation on poor prognosis samples. Finally, we propose strong conservation of MTSS1 alsoon the transcriptional level and predict novel transcriptional regulators. Our data highlight important targets for future studies on the role of MIM in different tissues and cancers. |
| Databáze: | OpenAIRE |
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