Inhibition of cathepsin B by caspase-3 inhibitors blocks programmed cell death in Arabidopsis

Abstract Programmed cell death (PCD) is used by plants for development and survival to biotic and abiotic stresses. The role of caspases in PCD is well established in animal cells. Over the past 15 years, the importance of caspase-3-like enzymatic activity for plant PCD completion has been widely documented despite the absence of caspase orthologues. In particular, caspase-3 inhibitors blocked nearly all plant PCD tested. Here, we affinity-purified a plant caspase-3-like activity using a biotin-labelled caspase-3 inhibitor and identified Arabidopsis thaliana cathepsin B3 (AtCathB3) by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Consistent with this, recombinant AtCathB3 was found to have caspase-3-like activity and to be inhibited by caspase-3 inhibitors. AtCathepsin B triple-mutant lines showed reduced caspase-3-like enzymatic activity and reduced labelling with activity-based caspase-3 probes. Importantly, AtCathepsin B triple mutants showed a strong reduction in the PCD induced by ultraviolet (UV), oxidative stress (H2O2, methyl viologen) or endoplasmic reticulum stress. Our observations contribute to explain why caspase-3 inhibitors inhibit plant PCD and provide new tools to further plant PCD research. The fact that cathepsin B does regulate PCD in both animal and plant cells suggests that this protease may be part of an ancestral PCD pathway pre-existing the plant/animal divergence that needs further characterisation.

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Calcium Signaling in Plant Programmed Cell Death

Cells ◽

10.3390/cells10051089 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1089

Author(s):

Huimin Ren ◽

Xiaohong Zhao ◽

Wenjie Li ◽

Jamshaid Hussain ◽

Guoning Qi ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Abiotic Stresses ◽

Animal Studies ◽

Future Research ◽

Significant Progress ◽

Biotic And Abiotic Stresses ◽

Stress Perception ◽

The Past

Programmed cell death (PCD) is a process intended for the maintenance of cellular homeostasis by eliminating old, damaged, or unwanted cells. In plants, PCD takes place during developmental processes and in response to biotic and abiotic stresses. In contrast to the field of animal studies, PCD is not well understood in plants. Calcium (Ca2+) is a universal cell signaling entity and regulates numerous physiological activities across all the kingdoms of life. The cytosolic increase in Ca2+ is a prerequisite for the induction of PCD in plants. Although over the past years, we have witnessed significant progress in understanding the role of Ca2+ in the regulation of PCD, it is still unclear how the upstream stress perception leads to the Ca2+ elevation and how the signal is further propagated to result in the onset of PCD. In this review article, we discuss recent advancements in the field, and compare the role of Ca2+ signaling in PCD in biotic and abiotic stresses. Moreover, we discuss the upstream and downstream components of Ca2+ signaling and its crosstalk with other signaling pathways in PCD. The review is expected to provide new insights into the role of Ca2+ signaling in PCD and to identify gaps for future research efforts.

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Correction to: Inhibition of cathepsin B by caspase-3 inhibitors blocks programmed cell death in Arabidopsis

Cell Death and Differentiation ◽

10.1038/s41418-018-0136-1 ◽

2018 ◽

Vol 25 (8) ◽

pp. 1532-1532 ◽

Cited By ~ 2

Author(s):

Y. Ge ◽

Y-M. Cai ◽

L. Bonneau ◽

V. Rotari ◽

A. Danon ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Cathepsin B ◽

Caspase 3

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Two proteases with caspase-3-like activity, cathepsin B and proteasome, antagonistically control ER-stress-induced programmed cell death in Arabidopsis

New Phytologist ◽

10.1111/nph.14676 ◽

2017 ◽

Vol 218 (3) ◽

pp. 1143-1155 ◽

Cited By ~ 21

Author(s):

Yao-Min Cai ◽

Jia Yu ◽

Yuan Ge ◽

Aleksandr Mironov ◽

Patrick Gallois

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Er Stress ◽

Cathepsin B ◽

Caspase 3

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Responses of Marine Diatom Skeletonema marinoi to Nutrient Deficiency: Programmed Cell Death

Applied and Environmental Microbiology ◽

10.1128/aem.02460-19 ◽

2019 ◽

Vol 86 (3) ◽

Cited By ~ 2

Author(s):

Hualong Wang ◽

Feng Chen ◽

Tiezhu Mi ◽

Qian Liu ◽

Zhigang Yu ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Enzymatic Activity ◽

Marine Environment ◽

Caspase 3 ◽

Marine Diatom ◽

Content Type ◽

Nutrient Limitations ◽

Insight Into ◽

Skeletonema Marinoi

ABSTRACT Diatoms are important phytoplankton and contribute greatly to the primary productivity of marine ecosystems. Despite the ecological significance of diatoms and the importance of programmed cell death (PCD) in the fluctuation of diatom populations, little is known about the molecular mechanisms of PCD triggered by different nutrient stresses. Here we describe the physiological, morphological, biochemical, and molecular changes in response to low levels of nutrients in the ubiquitous diatom Skeletonema marinoi. The levels of gene expression involved in oxidation resistance and PCD strongly increased upon nitrogen (N) or phosphorus (P) starvation. The enzymatic activity of caspase 3-like protein also increased. Differences in mRNA levels and protein activities were observed between the low-N and low-P treatments, suggesting that PCD could have a differential response to different nutrient stresses. When cultures were replete with N or P, the growth inhibition stopped. Meanwhile, the enzymatic activity of caspase 3-like protein and the number of cells with damaged membranes decreased. These results suggest that PCD is an important cell fate decision mechanism in the marine diatom S. marinoi. Our results provide important insight into how diatoms adjust phenotypic and genotypic features of their cell-regulated death programs when stressed by nutrient limitations. Overall, this study could allow us to better understand the molecular mechanism behind the formation and termination of diatom blooms in the marine environment. IMPORTANCE Our study showed how the ubiquitous diatom S. marinoi responded to different nutrient limitations with PCD in terms of physiological, morphological, biochemical, and molecular characteristics. Some PCD-related genes (PDCD4, GOX, and HSP90) induced by N deficiency were relatively upregulated compared to those induced by P deficiency. In contrast, the expression of the TSG101 gene in S. marinoi showed a clear and constant increase during P limitation compared to N limitation. These findings suggest that PCD is a complex mechanism involving several different proteins. The systematic mRNA level investigations provide new insight into understanding the oxidative stress- and cell death-related functional genes of diatoms involved in the response to nutrient fluctuations (N or P stress) in the marine environment.

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Faculty Opinions recommendation of New Arabidopsis thaliana cytochrome c partners: a look into the elusive role of cytochrome c in programmed cell death in plants.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718104360.793488383 ◽

2013 ◽

Author(s):

Daniel Gallie

Keyword(s):

Arabidopsis Thaliana ◽

Cell Death ◽

Cytochrome C ◽

Programmed Cell Death

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The role of programmed cell death ligand-1/ programmed cell death-1 (PD-L1/PD-1) in HPV-induced cervical cancer and potential for their use in blockade therapy

Current Medicinal Chemistry ◽

10.2174/0929867327666200128105459 ◽

2020 ◽

Vol 27 ◽

Cited By ~ 1

Author(s):

Lifang Zhang ◽

Yu Zhao ◽

Quanmei Tu ◽

Xiangyang Xue ◽

Xueqiong Zhu ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Immune Escape ◽

Hypoxia Inducible Factor ◽

Hpv Infection ◽

Advanced Cervical Cancer ◽

Cervical Carcinogenesis ◽

Programmed Cell Death 1

Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

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Ozone-Induced Cell Death in Tobacco Cultivar Bel W3 Plants. The Role of Programmed Cell Death in Lesion Formation

PLANT PHYSIOLOGY ◽

10.1104/pp.103.026591 ◽

2003 ◽

Vol 133 (3) ◽

pp. 1122-1134 ◽

Cited By ~ 123

Author(s):

Stefania Pasqualini ◽

Claudia Piccioni ◽

Lara Reale ◽

Luisa Ederli ◽

Guido Della Torre ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Lesion Formation ◽

Tobacco Cultivar

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RAD50 and RAD51 Define Two Pathways That Collaborate to Maintain Telomeres in the Absence of Telomerase

Genetics ◽

10.1093/genetics/152.1.143 ◽

1999 ◽

Vol 152 (1) ◽

pp. 143-152 ◽

Cited By ~ 12

Author(s):

Siyuan Le ◽

J Kent Moore ◽

James E Haber ◽

Carol W Greider

Keyword(s):

Cell Death ◽

Telomere Length ◽

Gene Conversion ◽

De Novo ◽

Dna Recombination ◽

Telomere Maintenance ◽

Triple Mutant ◽

Yeast Telomerase ◽

Telomere Lengthening

Abstract Telomere length is maintained by the de novo addition of telomere repeats by telomerase, yet recombination can elongate telomeres in the absence of telomerase. When the yeast telomerase RNA component, TLC1, is deleted, telomeres shorten and most cells die. However, gene conversion mediated by the RAD52 pathway allows telomere lengthening in rare survivor cells. To further investigate the role of recombination in telomere maintenance, we assayed telomere length and the ability to generate survivors in several isogenic DNA recombination mutants, including rad50, rad51, rad52, rad54, rad57, xrs2, and mre11. The rad51, rad52, rad54, and rad57 mutations increased the rate of cell death in the absence of TLC1. In contrast, although the rad50, xrs2, and mre11 strains initially had short telomeres, double mutants with tlc1 did not affect the rate of cell death, and survivors were generated at later times than tlc1 alone. While none of the double mutants of recombination genes and tlc1 (except rad52 tlc1) blocked the ability to generate survivors, a rad50 rad51 tlc1 triple mutant did not allow the generation of survivors. Thus RAD50 and RAD51 define two separate pathways that collaborate to allow cells to survive in the absence of telomerase.

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Cell Death and Metabolic Stress in Gymnodinium catenatum Induced by Allelopathy

Toxins ◽

10.3390/toxins13070506 ◽

2021 ◽

Vol 13 (7) ◽

pp. 506

Author(s):

Leyberth José Fernández-Herrera ◽

Christine Johanna Band-Schmidt ◽

Tania Zenteno-Savín ◽

Ignacio Leyva-Valencia ◽

Claudia Judith Hernández-Guerrero ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Protein Content ◽

Caspase 3 ◽

Cellular Stress ◽

Allelopathic Effect ◽

Sod Activity ◽

Free Media ◽

O2 Production ◽

Gymnodinium Catenatum

Allelopathy between phytoplankton species can promote cellular stress and programmed cell death (PCD). The raphidophyte Chattonella marina var. marina, and the dinoflagellates Margalefidinium polykrikoides and Gymnodinium impudicum have allelopathic effects on Gymnodinium catenatum; however, the physiological mechanisms are unknown. We evaluated whether the allelopathic effect promotes cellular stress and activates PCD in G. catenatum. Cultures of G. catenatum were exposed to cell-free media of C. marina var. marina, M. polykrikoides and G. impudicum. The mortality, superoxide radical (O2●−) production, thiobarbituric acid reactive substances (TBARS) levels, superoxide dismutase (SOD) activity, protein content, and caspase-3 activity were quantified. Mortality (between 57 and 79%) was registered in G. catenatum after exposure to cell-free media of the three species. The maximal O2●− production occurred with C. marina var. marina cell-free media. The highest TBARS levels and SOD activity in G. catenatum were recorded with cell-free media from G. impudicum. The highest protein content was recorded with cell-free media from M. polykrikoides. All cell-free media caused an increase in the activity of caspase-3. These results indicate that the allelopathic effect in G. catenatum promotes cell stress and caspase-3 activation, as a signal for the induction of programmed cell death.

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