B06 | The evolution of regulated necrotic cell death
Prof. Dr. Kay Hofmann
Institute for Genetics
University of Cologne
Contact: Kay.Hofmann(at)uni-koeln(dot)de
For more information visit: Hofmann lab
Abstract
RCD pathways are found in many phyla, ranging from developmentally programmed apoptosis in animals to cell-autonomous programmed necrosis pathways that limit the spread of biotrophic pathogens in multicellular assemblies. This project builds on own previous results and expands on the inter-phylum comparison of cell death pathways. The central goal of this project is to understand how different necrotic signalling pathways evolved from a pre-existing set of ancient protein modules and later added lineage-specific sub-pathways leading to their functional diversification.
Recent Publications
Project B06 Publications 2nd Funding Period 2024 - 2027
2024
Shen Q, Hasegawa K, Oelerich N, Prakken A, Tersch LW, Wang J, Reichhardt F, Tersch A, Choo JC, Timmers T, Hofmann K, Parker JE, Chai J, Maekawa T. Cytoplasmic calcium influx mediated by plant MLKLs confers TNL-triggered immunity. Cell Host Microbe. 2024 Mar 13:S1931-3128(24)00059-3. doi: 10.1016/j.chom.2024.02.016. Epub ahead of print. PMID: 38513655.
Project B06 Publications 1st Funding Period 2020 - 2023
2020
Mahdi, L.K., Huang, M., Zhang, X., Nakano, R.T., Kopp, L.B., Saur, I.M.L., Jacob, F., Kovacova, V., Lapin, D., Parker, J.E., Murphy, J.M., Hofmann, K., Schulze-Lefert, P., Chai, J., Maekawa, T. (2020) Discovery of a Family of Mixed Lineage Kinase Domain-like Proteins in Plants and Their Role in Innate Immune Signaling. Cell Host & Microbehttps://doi.org/10.1016/j.chom.2020.08.012
Project related Publications
1999 - 2019
Seenivasan, R., Hermanns, T., Blyszcz, T., Lammers, M., Praefcke, G.J.K., and Hofmann, K. (2019) Mechanism and chain-specificity of RNF216/TRIAD3, the ubiquitin ligase mutated in Gordon-Holmes Syndrome. Hum. Mol. Genet., doi: 10.1093/hmg/ddz098
Hermanns, T., Pichlo, C., Woiwode, I., Klopffleisch, K., Witting, K.F., Ovaa, H., Baumann, U., and Hofmann, K. (2018). A family of unconventional deubiquitinases with modular chain specificity determinants. Nature Commun. 9, 799.
Daskalov, A., Habenstein, B., Sabaté, R., Berbon, M., Martinez, D., Chaignepain, S., Coulary-Salin, B., Hofmann, K., Loquet, A., and Saupe, S.J. (2016). Identification of a novel cell death-inducing domain reveals that fungal amyloid-controlled programmed cell death is related to necroptosis. Proc. Natl. Acad. Sci. U.S.A. 113, 2720-2705.
Kajava, A.V., Klopffleisch, K., Chen, S., and Hofmann, K. (2014). Evolutionary link between metazoan RHIM motif and prion-forming domain of fungal heterokaryon incompatibility factor HET-s/HET-s. Sci. Rep. 4, 7436.
Rebsamen, M., Heinz, L.X., Meylan, E., Michallet, M.C., Schroder, K., Hofmann, K., Vazquez, J., Benedict, C.A., and Tschopp, J. (2009). DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB. EMBO Rep. 10, 916-922.
Meylan, E., Burns, K., Hofmann, K., Blancheteau, V., Martinon, F., Kelliher, M., and Tschopp, J. (2004). RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat. Immunol. 5, 503-507.
Hofmann, K. (1999). The modular nature of apoptotic signaling proteins. Cell. Mol. Life Sci. 55,1113-1128.
Hofmann, K., and Dixit, V.M. (1998). Ceramide in apoptosis. Trends Biochem. Sci. 23, 374-377.
Hofmann, K., Bucher, P., and Tschopp, J. (1997). The CARD domain: a new apoptotic signalling motif. Trends Biochem. Sci. 22, 155-156.
Mahdi,L.K., Huang, M., Zhang, X., Nakano R.-T., Kopp, L.B., Saur, I. M.-L., Jacob, F., Kovacova, V., Lapin, D., Murphy, J., Parker, J., Hofmann, K., Schulze-Lefert. P, Chai. J., and T. Maekawa (2019). Plant mixed lineage kinase domain-like proteins limit biotrophic pathogen growth, BioRxiv doi.org/10.1101/681015