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Identification of substrates of Citron kinase, a serine/threonine kinase involved in cell cycle and microcephaly

Supervisor: Dr Paolo D'Avino

Based at the Department of Pathology, Tennis Court Road

Citron kinase (CIT-K) is a multifunctional serine/threonine kinase that plays important roles in different aspects of the cell cycle, including DNA damage control, the orientation of the mitotic spindle and cytokinesis. In addition, mutations in CIT-K have been linked to the development of human primary microcephaly. However, the molecular mechanisms by which CIT-K-mediated phosphorylation regulates the cell cycle and affects human brain development are still not understood, mainly because its substrates have not been identified. To address this, we propose to use complementary and convergent experimental strategies that employ a combination of gene editing, chemical genetics and quantitative phospho-proteomics. 

 

Full details of the project can be found here.

 

Recent Publications

  • Bassi I.Z., Audusseau, M., Riparbelli, M.G., Callaini, G. and D’Avino P.P. (2013) Citron kinase controls a molecular network required for midbody formation in cytokinesis. Proceedings of the National Academy of Sciences USA, 110(24):9782-9787.
  • McKenzie C., Bassi I.Z., Debski, J., Gottardo M., Callaini, G., Dadlez, M. and D’Avino P.P. (2016) Cross-regulation between Aurora B and Citron kinase controls midbody architecture in cytokinesis. Open Biology, 6: 160019 (doi: 10.1098/rsob.160019).
  • Capalbo, L., Mela, I., Abad, M.A., Jeyaprakash A.A., Edwardson, J.M. and D’Avino P.P. (2016) Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis. Open Biology, 6: 160248 (doi: 10.1098/rsob.160248)
  • McKenzie, C. and D’Avino P.P. (2016) Investigating cytokinesis failure as a strategy in cancer therapy. Oncotarget, 7(52):87323-87341 (doi: 10.18632/oncotarget.13556)
  • D’Avino P.P. and Capalbo L. (2016) Regulation of midbody formation and function by mitotic kinases. Seminars in Cell and Developmental Biology, 53:57-63.
  • D’Avino P.P. (2017). Citron kinase - renaissance of a neglected mitotic kinase. Journal of Cell Science, 130(10): 1701-1708; doi: 10.1242/jcs.200253