Last changed: 04 September 2023

Proteases cleave polypeptide chains and, in this way, modulate activity of target proteins and downstream pathways. Our current efforts are to unravel structure-function relationships of metacaspases, a phylogenetically broad group of cysteine proteases representing ancestors of animal caspases. Metacaspases serve multiple and sometimes even antagonistic roles (e.g. as positive and negative regulators of cell death), but underlying molecular mechanisms, including biological substrates, remain poorly understood.

Our research is supported by the Knut and Alice Wallenberg (KAW) Foundation and the European Research Council (ERC)

Read more about this research at the KAW webpage here and there.

Read more on Dr. Simon Stael's innovative ERC project, DETOXPEST, that will leverage plant proteases to improve pesticide selectivity here.


Ongoing collaboration

Anna Linusson (Umeå University)

Jerry Ståhlberg (SLU)

Hannele Tuominen (SLU)

Núria Sánchez Coll (CRAG, Barcelona)

Marina Klemenčič (University of Ljubljana)

Thomas Nyström (Gothenburg University)

Marcin Poreba and Marcin Drag (Wroclaw University)

Frank van Breusegem (VIB, Ghent)

Selected publications

Selected publications:

Zou Y, Sabljić I, Horbach N, Dauphinee AN, Åsman A, Sancho Temino L, Minina EA, Drag M, Stael S, Poreba M, Ståhlberg J, Bozhkov PV. Thermoprotection by a cell membrane-localized metacaspase in a green alga. Plant Cell. 2024 Feb 26;36(3):665-687. 

Eisele-Bürger AM, Eisele F, Malmgren Hill S, Hao X, Schneider KL, Imamoglu R, Balchin D, Liu B, Hartl FU, Bozhkov PV, Nyström T. Calmodulin regulates protease versus co-chaperone activity of a metacaspase. Cell Rep. 2023 Nov 28;42(11):113372. 

Stael S, Sabljić I, Audenaert D, Andersson T, Tsiatsiani L, Kumpf RP, Vidal-Albalat A, Lindgren C, Vercammen D, Jacques S, Nguyen L, Njo M, Fernández-Fernández ÁD, Beunens T, Timmerman E, Gevaert K, Van Montagu M, Ståhlberg J, Bozhkov PV, Linusson A, Beeckman T, Van Breusegem F. 2023. Structure-function study of a Ca2+-independent metacaspase involved in lateral root emergence. Proc Natl Acad Sci USA. 120(22):e2303480120. 

Fernández-Fernández ÁD, Stael S, Van Breusegem F. 2023. Mechanisms controlling plant proteases and their substrates. Cell Death Differ. 30(4):1047-1058. 

Sabljić I, Zou Y, Klemenčič M, Funk C, Ståhlberg J, Bozhkov P. 2022. Expression and Purification of the Type II Metacaspase from a Unicellular Green Alga Chlamydomonas reinhardtii. Methods Mol Biol. 2447:13-20.

Zou Y and Bozhkov PV (2021) Chlamydomonas proteases: classification, phylogeny and molecular regulation. J Exp Bot DOI: 10.1093/jxb/erab383

Minina EA, Staal J, Alvarez VE, Berges JA, Berman-Frank I, Beyaert R, Bidle KD, Bornancin F, Casanova M, Cazzulo J, Choi CJ, Coll NS, Dixit VM, Dolinar M, Fasel N, Funk C, Gallois P, Gevaert K, Gutierrez-Beltran E, Hailfinger S, Klemencic M, Koonin EV, Krappmann D, Linusson A, Machado M, Madeo F, Megeney LA, Moschou PN, Mottram, JC, Nyström T, Osiewacz HD, Overall CM, Pandey KC, Ruland J, Salvesen GS, Shi Y, Smertenko A, Stael S, Ståhlberg J, Suarez MF, Thome M, Tuominen H, Van Breusegem F, van der Hoorn RAL, Vardi A, Zhivotovsky B, Lam E and Bozhkov PV (2020) Classification and Nomencalture of Metacaspases and Paracaspases: No More Confusion with Caspases. Molecular Cell 77, 927-929.

Minina EA, Moschou PN, and Bozhkov PV (2017) Limited and digestive proteolysis: crosstalk between evolutionary conserved pathways​. New Phytologist 215, 958–964.

Minina EA, Coll NS, Tuominen H and Bozhkov PV (2017) Metacaspases versus caspases in development and cell fate regulation. Cell Death and Differentiation 24, 1314–1325.

Moschou PN, Gutierrez-Beltran E, Bozhkov PV, Smertenko AP (2016) Separase Promotes Microtubule Polymerization by Activating CENP-E-Related Kinesin Kin7. Developmental Cell 37: 350-361.

Moschou PN, Savenkov EI, Minina EA, Fukada K, Reza SH, Gutierrez-Beltran E, Sanchez-Vera V, Suarez MF, Hussey P, Smertenko AP and Bozhkov PV (2016) EXTRA SPINDLE POLES (Separase) controls anisotropic cell expansion in Norway spruce (Picea abies) embryos independently from its role in anaphase progression. New Phytologist doi: 10.1111/nph.14012

P.V. Bozhkov and G. Salvesen (Editors). Caspases, Paracaspases and Metacaspases.Series: Methods in Molecular Biology, Vol. 1133 Humana Press. 2014. ISBN 978-1-4939-0356-6.
Minina E, Filonova L, Fukada K, Savenkov EI, Sanchez-Vera V, Suarez MF, Daniel G, Clapham D, Gogvadze V, Zhivotovsky B, Smertenko AP and Bozhkov PV (2013) Metacaspase and autophagy determine the mode of plant cell death. Journal of Cell Biology 203: 917-927 
Peng Zhao, Xue-mei Zhou, Li-yao Zhang, Wei Wang, Li-gang Ma, Li-bo Yang, Xiong-bo Peng, Bozhkov PV, Meng-xiang Sun. (2013) A bipartite molecular module controls cell death activation in the basal cell lineage of plant embryos. PLOS Biology 11(9): e1001655
Moschou PN, Smertenko AP, Fukada K, Savenkov EI, Minina EA, Robert S, Hussey PJ and Bozhkov PV (2013) The Caspase-Related Protease Separase (EXTRA SPINDLE POLES) Regulates Cell Polarity and Cytokinesis in Arabidopsis. Plant Cell 25: 2171-2186

Moschou PN and Bozhkov PV (2012) Separases: biochemistry and function. Physiologia Plantarum 145: 67-76.

Tsiatsiani L, Van Breusegem F, Gallois P, Zavialov A, Lam E and Bozhkov PV (2011) Metacaspases. Cell Death and Differentiation 18: 1279-1288.

Bozhkov PV, Smertenko AP and Zhivotovsky B (2010) Aspasing out metacaspases and caspases: proteases of many trades. Science Signaling, 3: pe48.

Sundström J, Vaculova A, Smertenko AP, Savenkov EI, Golovko A, Minina E, Tiwari BS, Rodriguez-Nieto S, Zamyatnin AAJr, Välineva T, Saarikettu J, Frilander MJ, Suarez MF, Zavialov A, Ståhl U, Hussey PJ, Silvennoinen O, Sundberg E, Zhivotovsky B, and Bozhkov PV (2009) Tudor staphylococcal nuclease is an evolutionarily conserved component of the programmed cell death degradome. Nature Cell Biology 11: 1347-1354. 

Bozhkov PV, Suarez MF, Filonova LH, Daniel G, Zamyatnin AA Jr, Rodriguez-Nieto S, Zhivotovsky B and Smertenko A. (2005) Cysteine protease mcII-Pa executes programmed cell death during plant embryogenesis. Proc Natl Acad Sci USA 102: 14463-14468.

Suarez MF, Filonova LH, Smertenko A, Savenkov EI, Clapham DH, von Arnold S, Zhivotovsky B and Bozhkov PV. (2004) Metacaspase-dependent programmed cell death is essential for plant embryogenesis. Current Biology 14: R339-R340. 

Bozhkov PV, Filonova LH, Suarez MF, Helmersson A, Smertenko AP, Zhivotovsky B and von Arnold S. (2004) VEIDase is a principal caspase-like activity involved in plant programmed cell death and essential for embryonic pattern formation. Cell Death and Differentiation. 11: 175-182.