RRC ID 79023
Author Shinoda N, Horikoshi M, Taira Y, Muramoto M, Hirayama S, Murata S, Miura M.
Title Caspase cleaves Drosophila BubR1 to modulate spindle assembly checkpoint function and lifespan of the organism.
Journal FEBS J
Abstract Caspases cleave over 1500 substrates in the human proteome in both lethal and non-lethal scenarios. However, reports of the physiological consequences of substrate cleavage are limited. Additionally, the manner in which caspase cleaves only a subset of substrates in the non-lethal scenario remains to be elucidated. BubR1, a spindle assembly checkpoint component, is a caspase substrate in humans, the physiological function of which remains unclear. Here, we found that caspases, especially Drice, cleave Drosophila BubR1 between the N-terminal KEN box motif and C-terminal kinase domain. By using proximity labelling, we found that Drice, but not Dcp-1, is in proximity to BubR1, suggesting that protein proximity facilitates substrate preference. The cleaved fragments displayed altered subcellular localization and protein-protein interactions. Flies that harboured cleavage-resistant BubR1 showed longer duration of BubR1 localization to the kinetochore upon colchicine treatment. Furthermore, these flies showed extended lifespan. Thus, we propose that the caspase-mediated cleavage of BubR1 limits spindle assembly checkpoint and organismal lifespan. Our results highlight the importance of the individual analysis of substrates in vivo to determine the biological significance of caspase-dependent non-lethal cellular processes.
Volume 290(17)
Pages 4200-4223
Published 2023-9-1
DOI 10.1111/febs.16811
PMID 37151120
MeSH Animals Caspases / genetics Caspases / metabolism Cell Cycle Proteins / genetics Drosophila* / genetics Drosophila* / metabolism Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Humans Longevity / genetics M Phase Cell Cycle Checkpoints / genetics Protein Serine-Threonine Kinases / metabolism Spindle Apparatus / genetics
Drosophila DGRC#102258 DGRC#102444 DGRC#150224