scholarly journals Pepper pathogenesis-related protein 4c is a plasma membrane-localized cysteine protease inhibitor that is required for plant cell death and defense signaling

2014 ◽  
Vol 81 (1) ◽  
pp. 81-94 ◽  
Author(s):  
Nak Hyun Kim ◽  
Byung Kook Hwang
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Protease Inhibitor ◽  
Plant Cell ◽  
Cysteine Protease ◽  
Cysteine Protease Inhibitor ◽  
Related Protein ◽  
Defense Signaling ◽  
Pathogenesis Related Protein ◽  
Pathogenesis Related

scholarly journals Cholic Acid, a Bile Acid Elicitor of Hypersensitive Cell Death, Pathogenesis-Related Protein Synthesis, and Phytoalexin Accumulation in Rice

2006 ◽  
Vol 140 (4) ◽  
pp. 1475-1483 ◽  
Author(s):  
Jinichiro Koga ◽  
Hidetoshi Kubota ◽  
Shuichi Gomi ◽  
Kenji Umemura ◽  
Masao Ohnishi ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Synthesis ◽  
Bile Acid ◽  
Cholic Acid ◽  
Related Protein ◽  
Hypersensitive Cell Death ◽  
Pathogenesis Related Protein ◽  
Pathogenesis Related

scholarly journals Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2

2012 ◽  
Vol 7 (3) ◽  
pp. 484-496 ◽  
Author(s):  
Likun Li ◽  
Guang Yang ◽  
Chengzhen Ren ◽  
Ryuta Tanimoto ◽  
Takahiro Hirayama ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Related Protein ◽  
Cancer Cell Death ◽  
Pathogenesis Related Protein ◽  
Pathogenesis Related

scholarly journals Exoerythrocytic Plasmodium Parasites Secrete a Cysteine Protease Inhibitor Involved in Sporozoite Invasion and Capable of Blocking Cell Death of Host Hepatocytes

2010 ◽  
Vol 6 (3) ◽  
pp. e1000825 ◽  
Author(s):  
Annika Rennenberg ◽  
Christine Lehmann ◽  
Anna Heitmann ◽  
Tina Witt ◽  
Guido Hansen ◽  
...  
Keyword(s):  
Cell Death ◽  
Protease Inhibitor ◽  
Cysteine Protease ◽  
Cysteine Protease Inhibitor

scholarly journals SerpinB3 drives cancer stem cell survival in glioblastoma

2021 ◽  
Author(s):  
Adam Lauko ◽  
Josephine Volovetz ◽  
Soumya M Turaga ◽  
Defne Bayik ◽  
Dennis C Watson ◽  
...  
Keyword(s):  
Cell Death ◽  
Protease Inhibitor ◽  
Cysteine Protease ◽  
Cathepsin L ◽  
Standard Of Care ◽  
Surface Expression ◽  
Therapeutic Interventions ◽  
Cysteine Protease Inhibitor ◽  
Cell Surface Expression ◽  
Downstream Signaling

Despite therapeutic interventions for glioblastoma (GBM), cancer stem cells (CSCs) drive recurrence. The precise mechanisms underlying CSC therapeutic resistance, namely inhibition of cell death, are unclear. We built on previous observations that the high cell surface expression of junctional adhesion molecule-A drives CSC maintenance and identified downstream signaling networks, including the cysteine protease inhibitor SerpinB3. Using genetic depletion approaches, we found that SerpinB3 is necessary for CSC maintenance, survival, and tumor growth, as well as CSC pathway activation. The knockdown of SerpinB3 also increased apoptosis and susceptibility to radiation therapy. Mechanistically, SerpinB3 was essential to buffer cathepsin L-mediated cell death, which was enhanced with radiation. Finally, we found that SerpinB3 knockdown dramatically increased the efficacy of radiation in pre-clinical models. Taken together, our findings identify a novel GBM CSC-specific survival mechanism involving a previously uninvestigated cysteine protease inhibitor, SerpinB3, and provide a potential target to improve the efficacy of standard-of-care GBM therapies against therapeutically resistant CSCs.

STEM-15. SerpinB3 DRIVES CANCER STEM CELL SURVIVAL IN GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi24-vi24
Author(s):  
Adam Lauko ◽  
Soumya M Turaga ◽  
Josephine Volovetz ◽  
Defne Bayik ◽  
Shideng Bao ◽  
...  
Keyword(s):  
Cell Death ◽  
Protease Inhibitor ◽  
Cysteine Protease ◽  
Xenograft Model ◽  
Standard Of Care ◽  
Therapeutic Interventions ◽  
Cysteine Protease Inhibitor ◽  
Orthotopic Xenograft Model

Abstract Despite therapeutic interventions for glioblastoma (GBM), self-renewing, therapy-resistant populations of cells referred to as cancer stem cells (CSCs) drive recurrence. Previously, we identified the unique expression of junctional adhesion molecule-A (JAM-A) on CSCs and demonstrated that JAM-A is both necessary and sufficient for self-renewal and tumor growth. Moreover, we determined that JAM-A signals via Akt in GBM CSCs to sustain pluripotency transcription factor activity; however, the entire signaling network has yet to be fully elucidated. To further delineate this pathway, we immunoprecipitated JAM-A from patient-derived GBM CSCs and performed mass spectrometry to determine JAM-A binding proteins. This led to the identification of the cysteine protease inhibitor SerpinB3 as a putative JAM-A binding partner. Using in vitro CSC functional assays, we show that SerpinB3 is necessary for CSC maintenance and survival. In an in vivo orthotopic xenograft model, knockdown of SerpinB3 extended survival. Mechanistically, knockdown of SerpinB3 led to decreased expression of TGF-β, Myc, WNT, and Notch signaling, known regulators of the CSC state. Additionally, knockdown of SerpinB3 increases susceptibility to radiation therapy. SerpinB3 is essential for buffering cells against cathepsin-mediated cell death, and we found that elevated lysosomal membrane permeability after radiation leads to cathepsin release into the cytoplasm. As a result, SerpinB3 knockdown cells have a diminished capacity to inhibit cathepsin-driven cell death after radiation. The addition of the cathepsin inhibitor E64D partially rescues the SerpinB3 knockdown, however, SerpinB3 mutants that are unable to inhibit cathepsins fail to do the same. Taken together, our findings, identify a novel GBM CSC-specific survival mechanism involving a previously uninvestigated cysteine protease inhibitor, SerpinB3, and provide a potential target to increase the efficacy of standard of care GBM therapies against therapy-resistant CSCs.

scholarly journals Maize death acids, 9-lipoxygenase–derived cyclopente(a)nones, display activity as cytotoxic phytoalexins and transcriptional mediators

2015 ◽  
Vol 112 (36) ◽  
pp. 11407-11412 ◽  
Author(s):  
Shawn A. Christensen ◽  
Alisa Huffaker ◽  
Fatma Kaplan ◽  
James Sims ◽  
Sebastian Ziemann ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Cysteine Protease ◽  
Helicoverpa Zea ◽  
Fusarium Verticillioides ◽  
Cysteine Protease Inhibitor ◽  
Pathogenesis Related ◽  
Genes Encoding ◽  
Protease Activation ◽  
Glutathione S Transferases ◽  
Related Proteins

Plant damage promotes the interaction of lipoxygenases (LOXs) with fatty acids yielding 9-hydroperoxides, 13-hydroperoxides, and complex arrays of oxylipins. The action of 13-LOX on linolenic acid enables production of 12-oxo-phytodienoic acid (12-OPDA) and its downstream products, termed “jasmonates.” As signals, jasmonates have related yet distinct roles in the regulation of plant resistance against insect and pathogen attack. A similar pathway involving 9-LOX activity on linolenic and linoleic acid leads to the 12-OPDA positional isomer, 10-oxo-11-phytodienoic acid (10-OPDA) and 10-oxo-11-phytoenoic acid (10-OPEA), respectively; however, physiological roles for 9-LOX cyclopentenones have remained unclear. In developing maize (Zea mays) leaves, southern leaf blight (Cochliobolus heterostrophus) infection results in dying necrotic tissue and the localized accumulation of 10-OPEA, 10-OPDA, and a series of related 14- and 12-carbon metabolites, collectively termed “death acids.” 10-OPEA accumulation becomes wound inducible within fungal-infected tissues and at physiologically relevant concentrations acts as a phytoalexin by suppressing the growth of fungi and herbivores including Aspergillus flavus, Fusarium verticillioides, and Helicoverpa zea. Unlike previously established maize phytoalexins, 10-OPEA and 10-OPDA display significant phytotoxicity. Both 12-OPDA and 10-OPEA promote the transcription of defense genes encoding glutathione S transferases, cytochrome P450s, and pathogenesis-related proteins. In contrast, 10-OPEA only weakly promotes the accumulation of multiple protease inhibitor transcripts. Consistent with a role in dying tissue, 10-OPEA application promotes cysteine protease activation and cell death, which is inhibited by overexpression of the cysteine protease inhibitor maize cystatin-9. Unlike jasmonates, functions for 10-OPEA and associated death acids are consistent with specialized roles in local defense reactions.

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