Functional Differences between FOXOs
Friday 23 January 2009
Prof.dr. Paul Coffer and drs. Kristan van der Vos
Project
Forkhead transcription factors (FOXOs) have been implicated as being critical in the regulation of diverse aspects of cellular physiology. In the presence of cytokines direct phosphorylation of FOXOs by protein kinase B (PKB/c-akt) leads to their transport from the nucleus to the cytoplasm and thereby their inactivation. In contrast, during cytokine deprivation, nuclear translocation of FOXOs leads to upregulation of genes involved in cell cycle arrest, apoptosis and differentiation.
In mammals three different FOXOs are expressed: FOXO1, FOXO3a and FOXO4. The DNA binding domain is conserved between these transcription factors, however outside this domain the FOXOs are not homologous. The aim of this research is to understand the functional differences between these transcription factors and determine whether they play specific roles in immune homeostasis.
To determine the precise functional role of each FOXO we want to compare the differences between activation of FOXO1, FOXO3a and FOXO4. In order to do this stable FOXO cell lines will be made and the effects of FOXO activation in terms of survival and proliferation will be analysed. Furthermore we will look at the molecular level to identify proteins interacting with and regulating the function of FOXO transcription factors.
Techniques
Cell culture, protein biochemistry, diverse molecular biological techniques, flowcytometry, cell culture, immunefluorescence
Duration
6-9 months
Contact
Drs. Kristan van der Vos, kvos3@umcutrecht.nl, 088 75 535 70
Prof.dr. Paul Coffer, p.j.coffer@umcutrecht.nl
Dr. Kristin Denzer, k.denzer@umcutrecht.nl, 088 75 576 73
More info / references
UMC website - Dept. of Immunology
Molecular immunology website
Coffer, P.J. and Burgering, B.M.T. (2004) Nature Immunol. Rev. 4, 889-899
Coffer, P.J. (2003) Trends Immunol. 24, 470-471
Birkenkamp, K.U. and Coffer, P.J. (2003) J. Immunol. 171, 1623-1629
Coffer, P.J. (2003) Science (STKE) 2003, pe39
Birkenkamp, K.U. and Coffer, P.J. (2003) Biochem Soc. Trans. 31, 292-297
back