ArticleCell death and differentiation2014
Granzyme M targets topoisomerase II alpha to trigger cell cycle arrest and caspase-dependent apoptosis.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- miR-30c-2-3p suppresses the proliferation of human renal cell carcinoma cells by targeting TOP2A.Asian biomedicine : research, reviews and news · 2023Article
- Review
- Noncytotoxic functions of killer cell granzymes in viral infections.PLoS pathogens · 2021Review
- Cytotoxic Lymphocytes Target HIV-1 Gag Through Granzyme M-Mediated Cleavage.Frontiers in immunology · 2021Article
- Auto-antibodies against apolipoprotein A-1 block cancer cells proliferation and induce apoptosis.Oncotarget · 2020Article
- Killer cell proteases can target viral immediate-early proteins to control human cytomegalovirus infection in a noncytotoxic manner.PLoS pathogens · 2020Article
- Resistance of HIV-infected macrophages to CD8Nature immunology · 2018Article
- Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2016Review
- Efficacy of traditional Chinese medicine in treating cancer.Biomedical reports · 2016Article
- Perforin and granzymes: function, dysfunction and human pathology.Nature reviews. Immunology · 2015Review
- NK cell intrinsic regulation of MIP-1α by granzyme M.Cell death & disease · 2014Article
- Granzyme M: behind enemy lines.Cell death and differentiation · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytotoxic lymphocyte protease granzyme M (GrM) is a potent inducer of tumor cell death. The apoptotic phenotype and mechanism by which it induces cell death, however, remain poorly understood and controversial. Here, we show that GrM-induced cell death was largely caspase-dependent with various hallmarks of classical apoptosis, coinciding with caspase-independent G2/M cell cycle arrest. Using positional proteomics in human tumor cells, we identified the nuclear enzyme topoisomerase II alpha (topoIIα) as a physiological substrate of GrM. Cleavage of topoIIα by GrM at Leu(1280) separated topoIIα functional domains from the nuclear localization signals, leading to nuclear exit of topoIIα catalytic activity, thereby rendering it nonfunctional. Similar to the apoptotic phenotype of GrM, topoIIα depletion in tumor cells led to cell cycle arrest in G2/M, mitochondrial perturbations, caspase activation, and apoptosis. We conclude that cytotoxic lymphocyte protease GrM targets topoIIα to trigger cell cycle arrest and caspase-dependent apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.