Faculty Opinions recommendation of Papain protects papaya trees from herbivorous insects: role of cysteine proteases in latex.

2004 ◽  
Author(s):  
Julia Kehr
Keyword(s):  
Cysteine Proteases ◽  
Herbivorous Insects

scholarly journals Papain protects papaya trees from herbivorous insects: role of cysteine proteases in latex

2004 ◽  
Vol 37 (3) ◽  
pp. 370-378 ◽  
Author(s):  
Kotaro Konno ◽  
Chikara Hirayama ◽  
Masatoshi Nakamura ◽  
Ken Tateishi ◽  
Yasumori Tamura ◽  
...  
Keyword(s):  
Cysteine Proteases ◽  
Herbivorous Insects

scholarly journals Loss of Non-Apoptotic Role of Caspase-3 in the PINK1 Mouse Model of Parkinson’s Disease

2019 ◽  
Vol 20 (14) ◽  
pp. 3407 ◽  
Author(s):  
Paola Imbriani ◽  
Annalisa Tassone ◽  
Maria Meringolo ◽  
Giulia Ponterio ◽  
Graziella Madeo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Caspase 3 ◽  
Cysteine Proteases ◽  
Synaptic Function ◽  
Adult Brain ◽  
Striatal Slices

Caspases are a family of conserved cysteine proteases that play key roles in multiple cellular processes, including programmed cell death and inflammation. Recent evidence shows that caspases are also involved in crucial non-apoptotic functions, such as dendrite development, axon pruning, and synaptic plasticity mechanisms underlying learning and memory processes. The activated form of caspase-3, which is known to trigger widespread damage and degeneration, can also modulate synaptic function in the adult brain. Thus, in the present study, we tested the hypothesis that caspase-3 modulates synaptic plasticity at corticostriatal synapses in the phosphatase and tensin homolog (PTEN) induced kinase 1 (PINK1) mouse model of Parkinson’s disease (PD). Loss of PINK1 has been previously associated with an impairment of corticostriatal long-term depression (LTD), rescued by amphetamine-induced dopamine release. Here, we show that caspase-3 activity, measured after LTD induction, is significantly decreased in the PINK1 knockout model compared with wild-type mice. Accordingly, pretreatment of striatal slices with the caspase-3 activator α-(Trichloromethyl)-4-pyridineethanol (PETCM) rescues a physiological LTD in PINK1 knockout mice. Furthermore, the inhibition of caspase-3 prevents the amphetamine-induced rescue of LTD in the same model. Our data support a hormesis-based double role of caspase-3; when massively activated, it induces apoptosis, while at lower level of activation, it modulates physiological phenomena, like the expression of corticostriatal LTD. Exploring the non-apoptotic activation of caspase-3 may contribute to clarify the mechanisms involved in synaptic failure in PD, as well as in view of new potential pharmacological targets.

scholarly journals Role of Papain-Like Cysteine Proteases in Plant Development

2018 ◽  
Vol 9 ◽  
Author(s):  
Huijuan Liu ◽  
Menghui Hu ◽  
Qi Wang ◽  
Lin Cheng ◽  
Zaibao Zhang
Keyword(s):  
Plant Development ◽  
Cysteine Proteases

Targeting Deubiquitylating Enzyme USP1 in Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1813-1813
Author(s):  
Deepika Sharma Das ◽  
Yan Song ◽  
Arghya Ray ◽  
Paul Richardson ◽  
Dharminder Chauhan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dna Repair ◽  
Cell Lines ◽  
Cancer Cell ◽  
Therapeutic Index ◽  
Cysteine Proteases ◽  
Dependent Manner ◽  
Healthy Donors ◽  
Reporter Assays

Abstract Introduction Proteasome inhibitor Bortezomib is effective therapy of relapsed/refractory and newly diagnosed multiple myeloma (MM); however, dose-limiting toxicities and the development of resistance limit its long-term utility. Importantly, the ability of bortezomib to overcome resistance to conventional therapies has validated therapeutically targeting the Ubiquitin Proteasome System (UPS), and suggested potential utility of inhibitors of other components of the UPS including deubiquitylating enzymes (DUBs). Therapeutic strategies directed against DUBs may allow for more specific targeting of the UPS, and therefore be less likely to have off-target activities with associated toxicities. Our prior studies have identified a role of USP7, USP14, and UCHL5 in MM pathogenesis, and provided the rationale for targeting these DUBs in MM (Chauhan et al., Cancer Cell 2012, 11:345-358; Tian et al., Blood 2014, 123:706-716). Among DUBs, USP1 regulates DNA repair and the Fanconi anemia pathway through its association with its WD40 binding partner UAF1, and through its deubiquitylation of two critical DNA repair proteins, FANCD2-Ub and PCNA-Ub. Here we examined the role of USP1 DUB in MM using both biochemical and RNA interference strategies. Methods We utilized MM cell lines, patient cells, and peripheral blood mononuclear cells (PBMCs) from normal healthy donors. Cell viability was assessed using WST and CellTiter-Glo assays. MM.1S MM cells were transiently transfected with control short interfering RNA (siRNA), USP1 ON TARGET plus SMART pool siRNA using the cell line Nucleofector Kit V. A biochemical inhibitor of USP1 SJB3-019A (SJB) was purchased from Medchem Express, USA. In vitro DUB enzymatic activity was assessed using Ubiquitin-AMC and Ubiquitin-Rhodamine assay kits, as well as Ub-CHOP-reporter and K48-linked Ubiquitin tetramers. Competitive Ub-VS probe labeling was performed, as previously described (Chauhan et al., Cancer Cell 2012, 11:345-358). Signal transduction pathways were evaluated using immunoblotting. Statistical significance of data was determined using a Student's t test. Results Immunoblot analyses show higher USP1 levels in MM cell lines and patient cells than normal cells.USP1-siRNA inhibited MM cell proliferation, which was rescued by transfection of USP1 (WT). Using Ub-Rhodamine, Ub-AMC, and Ub-EKL reporter assays, we found higher USP1 deubiquitylating activity in patient MM cells versus normal cells, suggesting a favorable therapeutic index for targeting USP1. Importantly, siRNA-knockdown of USP1 both promoted degradation of tumorigenic ID1 protein, and inhibited proliferation of bortezomib-resistant (ANBL-6.BR) MM cells, suggesting that novel agents targeting USP1 may overcome bortezomib resistance. We next examined the effects of USP1 inhibitor SJB3 on MM cell growth and survival in our models of MM. Analysis using Ub-Rhodamine, Ub-AMC, and Ub-EKL reporter assays in a panel of MM cell lines showed that SJB is a potent, specific, and selective inhibitor of USP1 DUB activity (EC50 = 50 ± 5.7 nM), which does not inhibit other DUBs (USP2/USP5/USP7/USP14) or other families of cysteine proteases (EC50>100 μM). SJB blocks labeling of USP1 with HA-Ub-VS probe in a concentration-dependent manner, but did not alter labeling of other DUBs with HA-Ub-VS. SJB inhibits USP1-mediated cleavage of K48 linked polyubiquitin chains, but not that mediated by USP2 or USP7. Treatment of MM cell lines (MM.1S, MM.1R, RPMI-8226, Dox-40, ARP1, KMS11, U266, ANBL6.WT, ANBL6.BR, and LR5) and primary patient cells for 24h significantly decreases their viability (IC50 range 100nM to 500nM) (p < 0.05; n=3) without markedly affecting PBMCs from normal healthy donors, suggesting specific anti-MM activity and a favorable therapeutic index for SJB. Tumor cells from 3 of 5 patients were obtained from patients whose disease was progressing while on bortezomib, dexamethasone, and lenalidomide therapies. Mechanistic studies show that SJB-triggered apoptosis is associated with degradation of USP1 and Id1 protein. Finally, combination of SJB with lenalidomide, pomalidomide, HDACi ACY-1215, or bortezomib both induces synergistic anti-MM activity and overcomes drug resistance. Conclusion Our preclinical studies provide the framework for clinical evaluation of USP1 inhibitors, alone or in combination, as a potential MM therapy. Disclosures Chauhan: Stemline Therapeutics: Consultancy.

Caspases: cellular demolition experts

2001 ◽  
Vol 29 (6) ◽  
pp. 696-702 ◽  
Author(s):  
E. M. Creagh ◽  
S. J. Martin
Keyword(s):  
Cytochrome C ◽  
Limited Proteolysis ◽  
Cysteine Proteases ◽  
Caspase Activation ◽  
Caspase Family ◽  
Hierarchical Nature ◽  
Caspase Cascade ◽  
Cellular Stresses ◽  
Pro Inflammatory Cytokines

Apoptosis is co-ordinated by a family of cysteine proteases, the caspases, that dismantle the cell by targeting a panoply of proteins for limited proteolysis. The mammalian caspase family contains 14 members, a subset of which participates in apoptosis, with the remainder likely to be involved in the processing of pro-inflammatory cytokines. Apical caspase activation events are typically initiated by adaptor molecules that promote caspase aggregation and facilitate caspase auto-activation. In contrast, distal caspase activation events are controlled by caspases activated earlier in the cascade. Many cellular stresses provoke apoptosis by damaging mitochondria which results in the release of factors [such as cytochrome c and SMAC (second mitochondrial-derived activator of caspase)/Diablo] that trigger caspase activation and cell death. Here, we discuss the hierarchical nature of the caspase cascade that is triggered upon the release of mitochondrial cytochrome c into the cytoplasm, and the role of specific caspases within this cascade in targeting proteins for degradation. Finally, feedback amplification loops and important control points within the caspase cascade will be discussed.

scholarly journals Defensive role of leaf trichomes in resistance to herbivorous insects in Datura stramonium

2001 ◽  
Vol 14 (3) ◽  
pp. 424-432 ◽  
Author(s):  
P. L. Valverde ◽  
J. Fornoni ◽  
J. NUNez-Farfan
Keyword(s):  
Datura Stramonium ◽  
Herbivorous Insects ◽  
Leaf Trichomes ◽  
Defensive Role

scholarly journals The role of cysteine proteases in hypoxia-induced rat renal proximal tubular injury.

1995 ◽  
Vol 92 (17) ◽  
pp. 7662-7666 ◽  
Author(s):  
C. L. Edelstein ◽  
E. D. Wieder ◽  
M. M. Yaqoob ◽  
P. E. Gengaro ◽  
T. J. Burke ◽  
...  
Keyword(s):  
Cysteine Proteases ◽  
Tubular Injury ◽  
Proximal Tubular ◽  
Renal Proximal Tubular
Sign in / Sign up

Export Citation Format

Share Document