Yogesh Kulathu's Research Group

Kulathu Lab Website | Pubmed | Biography


Ubiquitin signalling mechanisms

An important role for the ubiquitin system is in the quality control and degradation 
of misfolded and damaged proteins, a process central to maintaining proteostasis. Ubiquitylation also has important non-degradative roles in signalling pathways. One of the ways ubiquitylation is able to mediate such a diverse array of functions is because a range of different ubiquitin signals can be formed. How does the cellular machinery distinguish between different ubiquitin signals to orchestrate a specific response? And what regulatory mechanisms ensure that ubiquitin signals are tightly regulated?

Our lab is interested in understanding (i) how ubiquitylation regulates protein degradation and proteostasis, and (ii) how ubiquitin signalling regulates T-lymphocyte biology and immune responses. To address these fundamental questions, we combine structural, biochemical and genetic approaches to uncover and understand the underlying pathways and mechanisms.

Our research has provided insights into the assembly and recognition of different ubiquitin signals. We recently discovered novel regulators of protein degradation that are highly conserved in evolution. Failure to degrade proteins in a timely manner is the underlying cause 
of diseases such as cancer and neurodegeneration. By studying
 how ubiquitylation regulates protein degradation and proteostasis we hope to better understand the molecular causes of disease that we can exploit for the development of effective therapeutic strategies.

Kulathu Lab Group Photo

People

Soo Youn Choi | Postdoctoral Researcher
Yosua Kristariyanto | PhD Student
Dominika Kwasna | PhD Student
Sven M Lange | PhD Student
Pawel Leznicki | Postdoctoral Researcher
Stephen Matthews | Senior Research Associate
Jayaprakash Natarajan | PhD Student
Deepika Pathak | Postdoctoral Researcher
Joshua Peter | PhD Student
Marjorie Laure Petitjean | Postdoctoral Researcher
Syed Arif Abdul Rehman | Postdoctoral Researcher

Selected Publications

Leznicki P and Kulathu Y. (2017) Mechanisms of regulation and diversification of Deubiquitylating enzyme function J Cell Sci doi:10 1242/jcs.201855
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
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