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Contact Details

Phone
+64 3 479 7871
Email
catherine.day@otago.ac.nz
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 (below). This suggests an unexpected level of signalling complexity.

TRAF complexed with ubiquitin and E2

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.

Ark2C-RING complexed with ubiquitin and E2

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 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

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