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Contact Details

Phone
+64 3 479 7871
Email
catherine.day@otago.ac.nz

University Links

Position
Professor
Department
Department of Biochemistry
Qualifications
BSc(Hons) PhD(Massey)
Research summary
Molecular basis of signalling.

Research

Fine tuning signalling

Proteins regulate all cellular processes, with their activities often fine tuned by modification with other molecules after they have been made. One important modification that regulates protein function is ubiquitin. Aberrant addition of ubiquitin results in a range of diseases, including cancer and autoimmune diseases.

My research group is interested in understanding how the addition of ubiquitin regulates protein function. Our goal is to discover how the attachment of ubiquitin to proteins is regulated, and how this modification alters protein function.

We have focused on the RING E3 ligases, the proteins that specify the targets for ubiquitin addition. Using structural, biochemical and biophysical approaches we have discovered important regulatory mechanisms that provide insight into how information in cells is transmitted.

Current projects in my laboratory focus on:

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 TRAF6, a RING-E3, is regulated by RING dimerisation and that heterodimers can form. This suggests an unexpected level of signalling complexity.

Revealing how ubiquitin chains are assembled. The ubiquitylation machinery contains many ubiquitin-binding sites. For example Ark2C is activated by ubiquitin binding to the RING domain (below). We have several projects aimed at understanding how ubiquitin-binding by the E2/E3 ubiquiitn writing machines modulates assembly of ubiquitin chains.

We are always keen to collaborate on projects aimed at understanding how ubiquitin is regulated.

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

Middleton, A. J., Zhu, J., & Day, C. L. (2020). The RING domain of RING Finger 12 efficiently builds degradative ubiquitin chains. Journal of Molecular Biology, 432, 3790-3801. doi: 10.1016/j.jmb.2020.05.001

Budhidarmo, R., Zhu, J., Middleton, A. J., & Day, C. L. (2018). The RING domain of RING Finger 11 (RNF11) protein binds Ubc13 and inhibits formation of polyubiquitin chains. FEBS Letters, 592(8), 1434-1444. doi: 10.1002/1873-3468.13029

Middleton, A. J., Budhidarmo, R., Das, A., Zhu, J., Foglizzo, M., Mace, P. D., & Day, C. L. (2017). The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1. Nature Communications, 8, 1788. doi: 10.1038/s41467-017-01665-3

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

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., Zhu, J., & Day, C. L. (2020). The RING domain of RING Finger 12 efficiently builds degradative ubiquitin chains. Journal of Molecular Biology, 432, 3790-3801. doi: 10.1016/j.jmb.2020.05.001

Journal - Research Article

Budhidarmo, R., Zhu, J., Middleton, A. J., & Day, C. L. (2018). The RING domain of RING Finger 11 (RNF11) protein binds Ubc13 and inhibits formation of polyubiquitin chains. FEBS Letters, 592(8), 1434-1444. doi: 10.1002/1873-3468.13029

Journal - Research Article

Middleton, A. J., Budhidarmo, R., Das, A., Zhu, J., Foglizzo, M., Mace, P. D., & Day, C. L. (2017). The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1. Nature Communications, 8, 1788. doi: 10.1038/s41467-017-01665-3

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

Journal - Research Article

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

Journal - Research Article

Middleton, A. J., Wright, J. D., & Day, C. L. (2017). Regulation of E2s: A role for additional ubiquitin binding sites? Journal of Molecular Biology, 429(22), 3430-3440. doi: 10.1016/j.jmb.2017.06.008

Journal - Research Article

Foglizzo, M., & Day, C. L. (2019). E2 enzymes: Lessons in ubiquitin transfer from XLID patients. Nature Chemical Biology, 15(1), 6-7. doi: 10.1038/s41589-018-0191-4

Journal - Research Other

Foglizzo, M., Middleton, A. J., Burgess, A. E., Crowther, J. M., Dobson, R. C. J., Murphy, J. M., Day, C. L., & Mace, P. D. (2018). A bidentate Polycomb Repressive-Deubiquitinase complex is required for efficient activity on nucleosomes. Nature Communications, 9, 3932. doi: 10.1038/s41467-018-06186-1

Journal - Research Article

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(20), 4073-4086. doi: 10.1016/j.jmb.2016.07.025

Journal - Research Article

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

Journal - Research Article

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

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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

Journal - Research Article

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.

Journal - Research Article

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.

Journal - Research Article

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