Professor Yogesh Kulathu

Our laboratory is interested in understanding how signal transduction is mediated in cells by the posttranslational modification of proteins. A primary focus of the lab is the ubiquitin system where the attachment of ubiquitin can alter the function and fate of the modified protein. By using a multidisciplinary approach, we aim to get mechanistic insights into how fundamental cellular processes are modulated by ubiquitylation to maintain cellular homeostasis. Of late, we have also expanded our research into the poorly studied ubiquitin-like modifier UFM1 which is essential for protein biogenesis and endoplasmic reticulum homeostasis. We aim at getting detailed biochemical and molecular insights into these processes by focussing on the enzymes that add the modification, modules that recognize and decode the modification, and proteases which remove them.

At present, we have 3 focus areas of research in the lab:

1.  How do different ubiquitin signals couple to different signalling outcomes and how is ubiquitylation regulated by Deubiquitinases (DUBs)?
2. How are proteins modified with UFM1 and why is this modification essential to maintain ER homeostasis?
3. How are the IRAK kinases activated and regulated in innate immune signalling?

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Selected Recent Publications

• Lange SM, McFarland MR, Lamoliatte F, Kwasna D, Shen L, Wallace I, Cole I, Armstrong L, Knebel A, Johnson C, De Cesare V and Kulathu Y. (2023) Comprehensive approach to study branched ubiquitin chains reveals roles for K48-K63 branches in VCP/p97-related processes. Biorxiv https://doi.org/10.1101/2023.01.10.523363
• Millrine D, Peter JJ and Kulathu Y. (2023). A guide to UFMylation, an emerging posttranslational modification. FEBS J. (doi: 10.1111/febs.16730)
• Peter JJ, Magnussen HM, DaRosa PA, Millrine D, Matthews SP, Lamoliatte F, Sundaramoorthy R, Kopito R and Kulathu Y. (2022) Non canonical scaffold-type ligase complex mediates protein UFMylation. EMBO Journal. 41(21):e111015.
• Milrine D, Cummings T, Matthews SP, Peter JJ, Magnussen H, Maccartney T, Lamoliatte F, Knebel A and Kulathu Y. (2022) Human UFSP1 is an active protease that regulates UFM1 maturation and UFMylation. Cell Reports. 40(5):111168
• Lange SM, Armstrong L, Kulathu Y. (2022) “Deubiquitinases: from mechanisms to their inhibition by small molecules” Molecular Cell 82(1):15-29
• Abdul Rehman SA, Armstrong LA, Lange SM, Kristariyanto YA, Grawert TW, Knebel A, Svergun DI and Kulathu Y. (2021) “Mechanism of activation and regulation of Deubiquitinase activity in MINDY1 and MINDY2”. Molecular Cell 81(20): 4176-4190.
• Lange SM, Nelen MI, Cohen P, Kulathu Y. (2021) “Dimeric Structure of the Pseudokinase IRAK3 Suggests an Allosteric Mechanism for Negative Regulation”. Structure. 29(3):238-251
• Dominika Kwasna, Syed Arif Abdul Rehman, Jayaprakash Natarajan, Stephen Matthews, Ross Madden, Virginia De Cesare, Simone Weidlich, Satpal Virdee, Ivan Ahel, Ian Gibbs-Seymour, Yogesh Kulathu (2018) Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability Mol Cell. 70(1) 150-164.e6
• Kristariyanto, Y. A., Abdul Rehman, S. A., Weidlich, S., Knebel, A. and Kulathu, Y. (2017) A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin chains. EMBO Rep 18 392-402
• Leznicki P and Kulathu Y. (2017) Mechanisms of regulation and diversification of Deubiquitylating enzyme function J Cell Sci doi:10 1242/jcs.201855
• Abdul Rehman, S. A., Kristariyanto, Y. A., Choi, S. Y., Nkosi, P. J., Weidlich, S., Labib, K., Hofmann, K. and Kulathu, Y. (2016) MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes. Mol Cell 63 146-55
• Kristariyanto, Y. A., Abdul Rehman, S. A., Campbell, D. G., Morrice, N. A., Johnson, C., Toth, R., Kulathu, Y. (2015) K29-selective ubiquitin binding domain reveals structural basis of specificity and heterotypic nature of k29 polyubiquitin Mol Cell 58 83-94
• Kristariyanto, Y. A., Choi, S. Y., Rehman, S. A., Ritorto, M. S., Campbell, D. G., Morrice, N. A., Toth, R., Kulathu, Y. (2015) Assembly and structure of Lys33-linked polyubiquitin reveals distinct conformations Biochem J 467 345-352