A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Computational analysis of the evolutionarily conserved Missing In Metastasis/Metastasis Suppressor 1 gene predicts novel interactions, regulatory regions and transcriptional control
Tekijät: Petar Petrov, Alexey V. Sarapulov, Lel Eöry, Cristina Scielzo, Lydia Scarfò, Jacqueline Smith, David W. Burt, Pieta K. Mattila
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2019
Journal: Scientific Reports
Tietokannassa oleva lehden nimi: SCIENTIFIC REPORTS
Lehden akronyymi: SCI REP-UK
Artikkelin numero: ARTN 4155
Vuosikerta: 9
Sivujen määrä: 17
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-019-40697-1
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/40088803
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 previously unappreciated 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 also on 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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
