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Identification of Citron kinase substrates by using chemical genetics and quantitative phospho-proteomics

Supervisor: Dr Paolo D'Avino

Based at the Department of Pathology, Tennis Court Road

Citron kinase (CIT-K) is a serine/threonine kinase that plays important roles in different aspects of the cell cycle. Mutations in CIT-K cause human primary microcephaly and this kinase has been identified as a potential target in cancer therapy. Although the kinase domain of CIT-K is necessary for most of its functions and mutations impairing kinase activity cause human primary microcephaly, only one CIT-K substrate has been identified so far. The aim of this project is to employ a systematic and comprehensive approach, involving gene editing, chemical genetics and quantitative proteomics, to identify CIT-K substrates throughout the cell cycle.  

 

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