Accessibility Skip to Global Navigation Skip to Local Navigation Skip to Content Skip to Search Skip to Site Map Menu

Health Sciences profile

Professor Catherine Day

PositionProfessor and Head of Department
DepartmentDepartment of Biochemistry
QualificationsBSc(Hons) PhD(Massey)
Research summaryMolecular basis of signalling.

Research

My research group is interested in understanding how post-translational modifications regulate protein-protein interactions and cell signalling. The main goal of our current research is to discover how the attachment of ubiquitin to proteins is regulated, and how this modification alters protein function. Disruption of protein ubiquitylation results in a range of diseases, including cancer and autoimmune diseases. As a result, there is considerable potential for development of new therapeutics that modulate protein ubiquitylation. Our research is focused on elucidating the features that regulate ubiquitylation of proteins that are of clinical relevance.

Current projects in my laboratory largely focus on:

  1. Understanding how E3 ligases promote the attachment of ubiquitin. We have a number of projects aimed at elucidating how RING-E3 ligases are regulated. For example we recently showed that Arkadia and Ark2C, two RING-E3, are regulated by ubiquitin itself.
    model of Ark
  2. Revealing how ubiquitin chains are assembled. The ubiquitylation machinery contains many ubiquitin-binding sites (as illustrated in this figure) and we have several projects aimed at understanding how ubiquitin-binding enhances chain formation.
    E2 E3 Ubiquitin
    We use biochemical, structural and biophysical approaches to understand how proteins are modified by ubiquitin. We are always keen to collaborate to understand how proteins are regulated by ubiquitin.

Positions available

Enquiries about projects from prospective graduate students are welcome and should be sent to catherine.day@otago.ac.nz.

For information about scholarships for postgraduate students go to the University of Otago website otago.ac.nz/postgraduate

Funding

Funding for my research has been provided by the Marsden Fund (NZ), the Health Research Council of New Zealand, Lottery Health, Genesis Oncology and the University of Otago.

Publications

Wright, J. D., Mace, P. D., & Day, C. L. (2016). Noncovalent ubiquitin interactions regulate the catalytic activity of ubiquitin writers. Trends in Biochemical Sciences, 41(11), 924-937. doi: 10.1016/j.tibs.2016.08.003

Foglizzo, M., Middleton, A. J., & Day, C. L. (2016). Structure and function of the RING domains of RNF20 and RNF40, dimeric E3 ligases that monoubiquitylate histone H2B. Journal of Molecular Biology, 428(9), 4073-4086. doi: 10.1016/j.jmb.2016.07.025

Wright, J. D., Mace, P. D., & Day, C. L. (2016). Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase activity. Nature Structural & Molecular Biology, 23(1), 45-52. doi: 10.1038/nsmb.3142

Middleton, A. J., & Day, C. L. (2015). The molecular basis of lysine 48 ubiquitin chain synthesis by Ube2K. Scientific Reports, 5, 16793. doi: 10.1038/srep16793

Budhidarmo, R., & Day, C. L. (2014). The ubiquitin-associated domain of cellular inhibitor of apoptosis proteins facilitates ubiquitylation. Journal of Biological Chemistry, 289(37), 25721-25736. doi: 10.1074/jbc.M113.545475

Journal - Research Article

Wright, J. D., Mace, P. D., & Day, C. L. (2016). Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase activity. Nature Structural & Molecular Biology, 23(1), 45-52. doi: 10.1038/nsmb.3142

Foglizzo, M., Middleton, A. J., & Day, C. L. (2016). Structure and function of the RING domains of RNF20 and RNF40, dimeric E3 ligases that monoubiquitylate histone H2B. Journal of Molecular Biology, 428(9), 4073-4086. doi: 10.1016/j.jmb.2016.07.025

Wright, J. D., Mace, P. D., & Day, C. L. (2016). Noncovalent ubiquitin interactions regulate the catalytic activity of ubiquitin writers. Trends in Biochemical Sciences, 41(11), 924-937. doi: 10.1016/j.tibs.2016.08.003

Middleton, A. J., & Day, C. L. (2015). The molecular basis of lysine 48 ubiquitin chain synthesis by Ube2K. Scientific Reports, 5, 16793. doi: 10.1038/srep16793

Condon, S. M., Mitsuuchi, Y., Deng, Y., LaPorte, M. G., Rippin, S. R., Haimowitz, T., … Bettjeman, B., Cumming, M. H., … Day, C. L., & Chunduru, S. K. (2014). Birinapant, a Smac-mimetic with improved tolerability for the treatment of solid tumors and hematological malignancies. Journal of Medicinal Chemistry, 57(9), 3666-3677. doi: 10.1021/jm500176w

Budhidarmo, R., & Day, C. L. (2014). The ubiquitin-associated domain of cellular inhibitor of apoptosis proteins facilitates ubiquitylation. Journal of Biological Chemistry, 289(37), 25721-25736. doi: 10.1074/jbc.M113.545475

Schumacher, F.-R., Wilson, G., & Day, C. L. (2013). The N-terminal extension of UBE2E ubiquitin–conjugating enzymes limits chain assembly. Journal of Molecular Biology, 425, 4099-4111. doi: 10.1016/j.jmb.2013.06.039

Nakatani, Y., Kleffmann, T., Linke, K., Condon, S. M., Hinds, M. G., & Day, C. L. (2013). Regulation of ubiquitin transfer by XIAP, a dimeric RING E3 ligase. Biochemical Journal, 450(3), 629-638. doi: 10.1042/BJ20121702

Budhidarmo, R., Nakatani, Y., & Day, C. L. (2012). RINGs hold the key to ubiquitin transfer. Trends in Biochemical Sciences, 37(2), 58-65. doi: 10.1016/j.tibs.2011.11.001

Feltham, R., Bettjeman, B., Budhidarmo, R., Mace, P. D., Shirley, S., Condon, S. M., … Day, C. L. (2011). Smac mimetics activate the E3 ligase activity of cIAP1 protein by promoting RING domain dimerization. Journal of Biological Chemistry, 286(19), 17015-17028. doi: 10.1074/jbc.M111.222919

Lopez, J., John, S. W., Tenev, T., Rautureau, G. J. P., Hinds, M. G., Francalanci, F., … Day, C. L., & Meier, P. (2011). CARD-mediated autoinhibition of cIAP1's E3 ligase activity suppresses cell proliferation and migration. Molecular Cell, 42(5), 569-583. doi: 10.1016/j.molcel.2011.04.008

Feltham, R., Moulin, M., Vince, J. E., Mace, P. D., Wong, W. W.-L., Anderton, H., Day, C. L., … Silke, J. (2010). Tumor necrosis factor (TNF) signaling, but not TWEAK (TNF-like weak inducer of apoptosis)-triggered cIAP1 (cellular inhibitor of apoptosis protein 1) degradation, requires cIAP1 RING dimerization and E2 binding. Journal of Biological Chemistry, 285(23), 17525-17536. doi: 10.1074/jbc.M109.087635

Liew, C. W., Sun, H., Hunter, T., & Day, C. L. (2010). RING domain dimerization is essential for RNF4 function. Biochemical Journal, 431(1), 23-29. doi: 10.1042/BJ20100957

Risk, J. M., Laurie, R. E., Macknight, R. C., & Day, C. L. (2010). FRIGIDA and related proteins have a conserved central domain and family specific N- and C- terminal regions that are functionally important. Plant Molecular Biology, 73, 493-505. doi: 10.1007/s11103-010-9635-2

Mace, P. D., Smits, C., Vaux, D. L., Silke, J., & Day, C. L. (2010). Asymmetric recruitment of cIAPs by TRAF2. Journal of Molecular Biology, 400, 8-15. doi: 10.1016/j.jmb.2010.04.055

Mace, P. D., Shirley, S., & Day, C. L. (2010). Assembling the building blocks: Structure and function of inhibitor of apoptosis proteins. Cell Death & Differentiation, 17, 46-53. doi: 10.1038/cdd.2009.45

Dewson, G., Kratina, T., Czabotar, P., Day, C. L., Adams, J. M., & Kluck, R. M. (2009). Bak activation for apoptosis involves oligomerization of dimers via their α6 helices. Molecular Cell, 36(4), 696-703. doi: 10.1016/j.molcel.2009.11.008

Vince, J. E., Pantaki, D., Feltham, R., Mace, P. D., Cordier, S. M., Schmukle, A. C., … Day, C. L., … Silke, J. (2009). TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (TNF) to efficiently activate NF-κB and to prevent TNF-induced apoptosis. Journal of Biological Chemistry, 284(51), 35906-35915. doi: 10.1074/jbc.M109.072256

Risk, J. M., Day, C. L., & Macknight, R. C. (2009). Reevaluation of abscisic acid-binding assays shows that G-Protein-Coupled Receptor2 does not bind abscisic acid. Plant Physiology, 150(1), 6-11.

Mabbitt, P. D., Rautureau, G. J. P., Day, C. L., Wilbanks, S. M., Eaton-Rye, J. J., & Hinds, M. G. (2009). Solution structure of Psb27 from cyanobacterial photosystem II. Biochemistry, 48(37), 8771-8773. doi: 10.1021/bi901309c

Risk, J. M., Macknight, R. C., & Day, C. L. (2008). FCA does not bind abscisic acid. Nature, 456(7223), E5-E6.

Smits, C., Czabotar, P. E., Hinds, M. G., & Day, C. L. (2008). Structural plasticity underpins promiscuous binding of the prosurvival protein A1. Structure, 16(5), 818-829. doi: 10.1016/j.str.2008.02.009

Day, C. L., Smits, C., Fan, F. C., Lee, E. F., Fairlie, W. D., & Hinds, M. G. (2008). Structure of the BH3 domains from the p53-inducible BH3-only proteins Noxa and Puma in complex with Mcl-1. Journal of Molecular Biology, 380(5), 958-971. doi: 10.1016/j.jmb.2008.05.071

Linke, K., Mace, P. D., Smith, C. A., Vaux, D. L., Silke, J., & Day, C. L. (2008). Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans. Cell Death & Differentiation, 15(5), 841-848. doi: 10.1038/sj.cdd.4402309

Mace, P. D., Linke, K., Feltham, R., Schumacher, F.-R., Smith, C. A., Vaux, D. L., … Day, C. L. (2008). Structures of the cIAP2 RING domain reveal conformational changes associated with ubiquitin-conjugating enzyme (E2) recruitment. Journal of Biological Chemistry, 283(46), 31633-31640.

Hinds, M. G., Smits, C., Fredericks-Short, R., Risk, J. M., Bailey, M., Huang, D. C. S., & Day, C. L. (2007). Bim, Bad and Bmf: Intrinsically unstructured BH3-only proteins that undergo a localized conformational change upon binding to prosurvival Bcl-2 targets. Cell Death & Differentiation, 14, 128-136.

Czabotar, P. E., Lee, E. F., van Delft, M. F., Day, C. L., Smith, B. J., Huang, D. C. S., … Colman, P. M. (2007). Structural insights into the degradation of Mcl-1 induced by BH3 domains. PNAS, 104(15), 6217-6222.

van Delft, M. F., Wei, A. H., Mason, K. D., Vandenberg, C. J., Chen, L., Czabotar, P. E., … Day, C. L., … Huang, D. C. S. (2006). The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell, 10(5), 389-399.

More publications...