17 results on '"Amy, L."'
Search Results
2. The GTPase-activating protein p120RasGAP has an evolutionarily conserved 'FLVR-unique' SH2 domain
- Author
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Titus J. Boggon, Amy L. Stiegler, Rachel Jaber Chehayeb, and Jessica Wang
- Subjects
0301 basic medicine ,030102 biochemistry & molecular biology ,GTPase-activating protein ,Chemistry ,Phosphopeptide ,Stereochemistry ,p120 GTPase Activating Protein ,Isothermal titration calorimetry ,Cell Biology ,Crystallography, X-Ray ,SH2 domain ,Biochemistry ,Homology (biology) ,Protein–protein interaction ,Evolution, Molecular ,src Homology Domains ,03 medical and health sciences ,030104 developmental biology ,Protein structure ,Humans ,Editors' Picks ,Molecular Biology ,Proto-oncogene tyrosine-protein kinase Src - Abstract
The Src homology 2 (SH2) domain has a highly conserved architecture that recognizes linear phosphotyrosine motifs and is present in a wide range of signaling pathways across different evolutionary taxa. A hallmark of SH2 domains is the arginine residue in the conserved FLVR motif that forms a direct salt bridge with bound phosphotyrosine. Here, we solve the X-ray crystal structures of the C-terminal SH2 domain of p120RasGAP (RASA1) in its apo and peptide-bound form. We find that the arginine residue in the FLVR motif does not directly contact pTyr(1087) of a bound phosphopeptide derived from p190RhoGAP; rather, it makes an intramolecular salt bridge to an aspartic acid. Unexpectedly, coordination of phosphotyrosine is achieved by a modified binding pocket that appears early in evolution. Using isothermal titration calorimetry, we find that substitution of the FLVR arginine R377A does not cause a significant loss of phosphopeptide binding, but rather a tandem substitution of R398A (SH2 position βD4) and K400A (SH2 position βD6) is required to disrupt the binding. These results indicate a hitherto unrecognized diversity in SH2 domain interactions with phosphotyrosine and classify the C-terminal SH2 domain of p120RasGAP as “FLVR-unique.”
- Published
- 2020
3. The conserved C-terminus of Sss1p is required to maintain the endoplasmic reticulum permeability barrier
- Author
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Robert F. L. Steuart, Kofi L. P. Stevens, Carl J. Mousley, Paris F. White, Hasindu G. Dassanayake, Aleshanee L. Paxman, Lamprini Baklous, Christopher M. Witham, Benjamin L. Schulz, Colin J. Stirling, and Amy L. Black
- Subjects
0301 basic medicine ,Sec61 ,Saccharomyces cerevisiae Proteins ,Saccharomyces cerevisiae ,Gating ,Endoplasmic Reticulum ,Biochemistry ,Permeability ,03 medical and health sciences ,Translocase ,Amino Acid Sequence ,Molecular Biology ,Integral membrane protein ,Secretory pathway ,030102 biochemistry & molecular biology ,biology ,Chemistry ,Endoplasmic reticulum ,C-terminus ,Cell Biology ,Endoplasmic Reticulum Stress ,Translocon ,Cell biology ,Protein Transport ,030104 developmental biology ,Multiprotein Complexes ,Protein Biosynthesis ,Mutation ,biology.protein ,SEC Translocation Channels - Abstract
The endoplasmic reticulum (ER) is the entry point to the secretory pathway and major site of protein biogenesis. Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the evolutionarily conserved Sec61 complex, a heterotrimeric channel that comprises the Sec61p/Sec61α, Sss1p/Sec61γ, and Sbh1p/Sec61β subunits. In addition to forming a protein-conducting channel, the Sec61 complex also functions to maintain the ER permeability barrier, preventing the mass free flow of essential ER-enriched molecules and ions. Loss in Sec61 integrity is detrimental and implicated in the progression of disease. The Sss1p/Sec61γ C terminus is juxtaposed to the key gating module of Sec61p/Sec61α, and we hypothesize it is important for gating the ER translocon. The ER stress response was found to be constitutively induced in two temperature-sensitive sss1 mutants (sss1(ts)) that are still proficient to conduct ER translocation. A screen to identify intergenic mutations that allow for sss1(ts) cells to grow at 37 °C suggests the ER permeability barrier to be compromised in these mutants. We propose the extreme C terminus of Sss1p/Sec61γ is an essential component of the gating module of the ER translocase and is required to maintain the ER permeability barrier.
- Published
- 2020
4. Extracellular cathepsin Z signals through the α5 integrin and augments NLRP3 inflammasome activation
- Author
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Campden, Rhiannon I., primary, Warren, Amy L., additional, Greene, Catherine J., additional, Chiriboga, Jose A., additional, Arnold, Corey R., additional, Aggarwal, Devin, additional, McKenna, Neil, additional, Sandall, Christina F., additional, MacDonald, Justin A., additional, and Yates, Robin M., additional
- Published
- 2021
- Full Text
- View/download PDF
5. Loss of the tumor suppressor BIN1 enables ATM Ser/Thr kinase activation by the nuclear protein E2F1 and renders cancer cells resistant to cisplatin
- Author
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Slovénie Pyndiah, Daitoku Sakamuro, Amy L. Abdulovic-Cui, Erica K. Cassimere, Watson P. Folk, Joanna C. Johnson, Alpana Kumari, and Tetsushi Iwasaki
- Subjects
0301 basic medicine ,DNA Repair ,Transcription, Genetic ,Tumor suppressor gene ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,DNA and Chromosomes ,Biochemistry ,Histones ,03 medical and health sciences ,Cell Line, Tumor ,Neoplasms ,medicine ,Humans ,E2F1 ,DNA Breaks, Double-Stranded ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,E2F2 ,Cisplatin ,MRE11 Homologue Protein ,030102 biochemistry & molecular biology ,Chemistry ,Tumor Suppressor Proteins ,Nuclear Proteins ,DNA, Neoplasm ,Cell Biology ,G2-M DNA damage checkpoint ,medicine.disease ,Acid Anhydride Hydrolases ,Cell biology ,MDC1 ,DNA-Binding Proteins ,DNA Repair Enzymes ,030104 developmental biology ,MRN complex ,Drug Resistance, Neoplasm ,Ataxia-telangiectasia ,biological phenomena, cell phenomena, and immunity ,E2F1 Transcription Factor ,Signal Transduction ,medicine.drug - Abstract
The tumor suppressor bridging integrator 1 (BIN1) is a corepressor of the transcription factor E2F1 and inhibits cell-cycle progression. BIN1 also curbs cellular poly(ADP-ribosyl)ation (PARylation) and increases sensitivity of cancer cells to DNA-damaging therapeutic agents such as cisplatin. However, how BIN1 deficiency, a hallmark of advanced cancer cells, increases cisplatin resistance remains elusive. Here, we report that BIN1 inactivates ataxia telangiectasia–mutated (ATM) serine/threonine kinase, particularly when BIN1 binds E2F1. BIN1 + 12A (a cancer-associated BIN1 splicing variant) also inhibited cellular PARylation, but only BIN1 increased cisplatin sensitivity. BIN1 prevented E2F1 from transcriptionally activating the human ATM promoter, whereas BIN1 + 12A did not physically interact with E2F1. Conversely, BIN1 loss significantly increased E2F1-dependent formation of MRE11A/RAD50/NBS1 DNA end-binding protein complex and efficiently promoted ATM autophosphorylation. Even in the absence of dsDNA breaks (DSBs), BIN1 loss promoted ATM-dependent phosphorylation of histone H2A family member X (forming γH2AX, a DSB biomarker) and mediator of DNA damage checkpoint 1 (MDC1, a γH2AX-binding adaptor protein for DSB repair). Of note, even in the presence of transcriptionally active (i.e. proapoptotic) TP53 tumor suppressor, BIN1 loss generally increased cisplatin resistance, which was conversely alleviated by ATM inactivation or E2F1 reduction. However, E2F2 or E2F3 depletion did not recapitulate the cisplatin sensitivity elicited by E2F1 elimination. Our study unveils an E2F1-specific signaling circuit that constitutively activates ATM and provokes cisplatin resistance in BIN1-deficient cancer cells and further reveals that γH2AX emergence may not always reflect DSBs if BIN1 is absent.
- Published
- 2019
6. Extracellular cathepsin Z signals through the α5 integrin and augments NLRP3 inflammasome activation
- Author
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Justin A. MacDonald, Catherine J. Greene, Christina F. Sandall, Neil McKenna, Rhiannon I. Campden, Jose A. Chiriboga, Robin M. Yates, Devin Aggarwal, Amy L. Warren, and Corey R. Arnold
- Subjects
Inflammasomes ,Interleukin-1beta ,Integrin alpha5 ,Biochemistry ,Mice ,0302 clinical medicine ,0303 health sciences ,biology ,Chemistry ,interleukin-1 (IL-1) ,Inflammasome ,Silicon Dioxide ,PMA, phorbol myristate acetate ,Cysteine protease ,3. Good health ,Cell biology ,silica ,LPS, lipopolysaccharide ,medicine.symptom ,RGD, arginine-glycine-asparigine ,Research Article ,medicine.drug ,integrin ,Silicosis ,Integrin ,Inflammation ,MSU, monosodium urate ,MS, multiple sclerosis ,EAE, encephalomyelitis ,03 medical and health sciences ,NLRP3 ,FBS, fetal bovine serum ,inflammasome ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Extracellular ,Animals ,APC, antigen-presenting cells ,Molecular Biology ,BMDC, bone marrow-derived dendritic cells ,030304 developmental biology ,Cathepsin ,Cathepsin Z ,Cell Biology ,arginine-glycine-aspartic acid (RGD) domain ,Cell culture ,biology.protein ,030217 neurology & neurosurgery - Abstract
Respiratory silicosis is a preventable occupational disease that develops secondary to the aspiration of crystalline silicon dioxide (silica) into the lungs, activation of the NLRP3 inflammasome, and IL-1β production. Cathepsin Z has been associated with the development of inflammation and IL-1β production; however, the mechanism of how cathepsin Z leads to IL-1β production is unknown. Here, the requirement for cathepsin Z in silicosis was determined using wildtype mice and mice deficient in cathepsin Z. The activation of the NLRP3 inflammasome in macrophages was studied using wildtype and cathepsin Z-deficient bone marrow-derived murine dendritic cells and the human monocytic cell line THP-1. Cells were activated with silica, and IL-1β release was determined using enzyme-linked immunosorbent assay or IL-1β bioassays. The relative contribution of the active domain or integrin-binding domain of cathepsin Z was studied using recombinant cathepsin Z constructs and the α5 integrin neutralizing antibody. We report that the lysosomal cysteine protease cathepsin Z potentiates the development of inflammation associated with respiratory silicosis by augmenting NLRP3 inflammasome-derived IL-1β expression in response to silica. Secreted cathepsin Z functions non-proteolytically via the internal integrin-binding domain to impact caspase-1 activation and the production of active IL-1β through integrin α5 without affecting transcription levels of NLRP3 inflammasome components. This work reveals a regulatory pathway for the NLRP3 inflammasome that occurs in an outside-in fashion and provides a link between extracellular cathepsin Z and inflammation. Furthermore, it reveals a level of NLRP3 inflammasome regulation that has previously only been found downstream of extracellular pathogens.
- Published
- 2022
7. TNF receptor-associated factor 3 restrains B-cell receptor signaling in normal and malignant B cells
- Author
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Whillock, Amy L., primary, Ybarra, Tiffany K., additional, and Bishop, Gail A., additional
- Published
- 2021
- Full Text
- View/download PDF
8. Extracellular cathepsin Z signals through the α5 integrin and augments NLRP3 inflammasome activation.
- Author
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Campden, Rhiannon I., Warren, Amy L., Greene, Catherine J., Chiriboga, Jose A., Arnold, Corey R., Aggarwal, Devin, McKenna, Neil, Sandall, Christina F., MacDonald, Justin A., and Yates, Robin M.
- Subjects
- *
NLRP3 protein , *INFLAMMASOMES , *ENZYME-linked immunosorbent assay , *OCCUPATIONAL diseases , *DENDRITIC cells , *ELASTASES , *INTEGRINS - Abstract
Respiratory silicosis is a preventable occupational disease that develops secondary to the aspiration of crystalline silicon dioxide (silica) into the lungs, activation of the NLRP3 inflammasome, and IL-1β production. Cathepsin Z has been associated with the development of inflammation and IL-1β production; however, the mechanism of how cathepsin Z leads to IL-1β production is unknown. Here, the requirement for cathepsin Z in silicosis was determined using WT mice and mice deficient in cathepsin Z. The activation of the NLRP3 inflammasome in macrophages was studied using WT and cathepsin Z-deficient bone marrow-derived murine dendritic cells and the human monocytic cell line THP-1. The cells were activated with silica, and IL-1β release was determined using enzyme-linked immunosorbent assay or IL-1β bioassays. The relative contribution of the active domain or integrin-binding domain of cathepsin Z was studied using recombinant cathepsin Z constructs and the α5 integrin neutralizing antibody. We report that the lysosomal cysteine protease cathepsin Z potentiates the development of inflammation associated with respiratory silicosis by augmenting NLRP3 inflammasome-derived IL-1β expression in response to silica. The secreted cathepsin Z functions nonproteolytically via the internal integrin-binding domain to impact caspase-1 activation and the production of active IL-1β through integrin α5 without affecting the transcription levels of NLRP3 inflammasome components. This work reveals a regulatory pathway for the NLRP3 inflammasome that occurs in an outside-in fashion and provides a link between extracellular cathepsin Z and inflammation. Furthermore, it reveals a level of NLRP3 inflammasome regulation that has previously only been found downstream of extracellular pathogens. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
9. The GTPase-activating protein p120RasGAP has an evolutionarily conserved “FLVR-unique” SH2 domain
- Author
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Jaber Chehayeb, Rachel, primary, Wang, Jessica, additional, Stiegler, Amy L., additional, and Boggon, Titus J., additional
- Published
- 2020
- Full Text
- View/download PDF
10. The conserved C-terminus of Sss1p is required to maintain the endoplasmic reticulum permeability barrier
- Author
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Witham, Christopher M., primary, Dassanayake, Hasindu G., additional, Paxman, Aleshanee L., additional, Stevens, Kofi L.P., additional, Baklous, Lamprini, additional, White, Paris F., additional, Black, Amy L., additional, Steuart, Robert F.L., additional, Stirling, Colin J., additional, Schulz, Benjamin L., additional, and Mousley, Carl J., additional
- Published
- 2020
- Full Text
- View/download PDF
11. TNF receptor-associated factor 3 restrains B-cell receptor signaling in normal and malignant B cells
- Author
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Gail A. Bishop, Amy L. Whillock, and Tiffany K. Ybarra
- Subjects
Male ,0301 basic medicine ,T-Lymphocytes ,Syk ,NIK, NF-κB-inducing kinase ,Biochemistry ,WB, western blot ,immunology ,B-cell receptor (BCR) ,Mice ,hemic and lymphatic diseases ,TRAF, TNF receptor-associated factor ,Agammaglobulinaemia Tyrosine Kinase ,Phosphorylation ,BAFF, B-cell activating factor ,Ub, ubiquitin ,Mice, Knockout ,TNF, tumor necrosis factor ,B-Lymphocytes ,biology ,Chemistry ,BCR, B-cell antigen receptor ,breakpoint cluster region ,PLCγ, phospholipase C gamma ,STAT, signal transducer and activator of transcription ,Btk ,TNF Receptor-Associated Factor 3 ,inhibition mechanism ,Lyn, Lck/yes novel tyrosine kinase ,Female ,WCL, whole-cell lysate ,MZ, marginal zone ,DLBCL, diffuse large B-cell lymphoma ,CD79 Antigens ,Research Article ,TLR, Toll-like receptor ,Signal Transduction ,Cell signaling ,LMP1, latent membrane protein 1 ,Syk, spleen-associated tyrosine kinase ,Receptors, Antigen, B-Cell ,lymphoma ,lymphocyte ,Btk, Bruton's tyrosine kinase ,SEM, standard error of the mean ,spleen tyrosine kinase (Syk) ,Erk, extracellular signal-regulated kinase ,03 medical and health sciences ,SHP, Src homology region 2 domain-containing phosphatase ,LYN ,cell signaling ,Animals ,Syk Kinase ,FO, follicular ,Molecular Biology ,TNF receptor-associated factor (TRAF) ,IκBα, NF-κB inhibitor alpha ,CD40 ,030102 biochemistry & molecular biology ,PI3K, phosphatidyl inositol-3 kinase ,T-cell receptor ,ITAM, immunoreceptor tyrosine-based activation motif ,Cell Biology ,TNF Receptor-Associated Factor 2 ,MAPK ,SHIP, SH2 domain-containing inositol polyphosphate 5-phosphatase ,Mice, Inbred C57BL ,030104 developmental biology ,TCR, T-cell receptor ,biology.protein ,Cancer research ,BCM, B-cell medium ,MAPK, mitogen-activated protein kinase ,CD80 - Abstract
TRAF3 has diverse signaling functions, which vary by cell type. Uniquely in B lymphocytes, TRAF3 inhibits homeostatic survival. Highlighting the role of TRAF3 as a tumor suppressor, loss-of-function TRAF3 mutations are associated with human B-cell malignancies, while B-cell-specific deletion of TRAF3 in mice leads to autoimmunity and lymphoma development. The role of TRAF3 in inhibiting noncanonical NF-κB activation, CD40 and BAFF-R signaling to B cells is well documented. In contrast, TRAF3 enhances many T-cell effector functions, through associating with and enhancing signaling by the T-cell receptor (TCR)-CD28 complex. The present study was designed to determine the role of TRAF3 in signaling via the B-cell antigen receptor (BCR). The BCR is crucial for antigen recognition, survival, proliferation, and antibody production, and defects in BCR signaling can promote abnormal survival of malignant B cells. Here, we show that TRAF3 is associated with both CD79B and the BCR-activated kinases Syk and Btk following BCR stimulation. BCR-induced phosphorylation of Syk and additional downstream kinases was increased in TRAF3−/− B cells, with regulation observed in both follicular and marginal zone B-cell subsets. BCR stimulation of TRAF3−/− B cells resulted in increased surface expression of MHC-II, CD80, and CD86 molecules. Interestingly, increased survival of TRAF3−/− primary B cells was resistant to inhibition of Btk, while TRAF3-deficient malignant B-cell lines showed enhanced sensitivity. TRAF3 serves to restrain normal and malignant BCR signaling, with important implications for its role in normal B-cell biology and abnormal survival of malignant B cells.
- Published
- 2021
12. Loss of the tumor suppressor BIN1 enables ATM Ser/Thr kinase activation by the nuclear protein E2F1 and renders cancer cells resistant to cisplatin
- Author
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Folk, Watson P., primary, Kumari, Alpana, additional, Iwasaki, Tetsushi, additional, Pyndiah, Slovénie, additional, Johnson, Joanna C., additional, Cassimere, Erica K., additional, Abdulovic-Cui, Amy L., additional, and Sakamuro, Daitoku, additional
- Published
- 2019
- Full Text
- View/download PDF
13. Structural Determinants for Binding of Sorting Nexin 17 (SNX17) to the Cytoplasmic Adaptor Protein Krev Interaction Trapped 1 (KRIT1)
- Author
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Weizhi Liu, Amy L. Stiegler, Rong Zhang, and Titus J. Boggon
- Subjects
Models, Molecular ,Endosome ,Sorting Nexins ,Amino Acid Motifs ,Immunoblotting ,Plasma protein binding ,Biology ,Crystallography, X-Ray ,Binding, Competitive ,Biochemistry ,Protein–protein interaction ,Proto-Oncogene Proteins ,Protein Interaction Mapping ,Humans ,Amino Acid Sequence ,Structural motif ,KRIT1 Protein ,Molecular Biology ,Binding Sites ,Sequence Homology, Amino Acid ,FERM domain ,Signal transducing adaptor protein ,Cell Biology ,Protein Structure, Tertiary ,Cell biology ,P-Selectin ,Sorting nexin ,Protein Structure and Folding ,Mutagenesis, Site-Directed ,Microtubule-Associated Proteins ,Protein Binding - Abstract
Sorting nexin 17 (SNX17) is a member of the family of cytoplasmic sorting nexin adaptor proteins that regulate endosomal trafficking of cell surface proteins. SNX17 localizes to early endosomes where it directly binds NPX(Y/F) motifs in the cytoplasmic tails of its target receptors to mediate their rates of endocytic internalization, recycling, and/or degradation. SNX17 has also been implicated in mediating cell signaling and can interact with cytoplasmic proteins. KRIT1 (Krev interaction trapped 1), a cytoplasmic adaptor protein associated with cerebral cavernous malformations, has previously been shown to interact with SNX17. Here, we demonstrate that SNX17 indeed binds directly to KRIT1 and map the binding to the second Asn-Pro-Xaa-Tyr/Phe (NPX(Y/F)) motif in KRIT1. We further characterize the interaction as being mediated by the FERM domain of SNX17. We present the co-crystal structure of SNX17-FERM with the KRIT1-NPXF2 peptide to 3.0 Å resolution and demonstrate that the interaction is highly similar in structure and binding affinity to that between SNX17 and P-selectin. We verify the molecular details of the interaction by site-directed mutagenesis and pulldown assay and thereby confirm that the major binding site for SNX17 is confined to the NPXF2 motif in KRIT1. Taken together, our results verify a direct interaction between SNX17 and KRIT1 and classify KRIT1 as a SNX17 binding partner.
- Published
- 2014
14. Structural Basis for the Disruption of the Cerebral Cavernous Malformations 2 (CCM2) Interaction with Krev Interaction Trapped 1 (KRIT1) by Disease-associated Mutations
- Author
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Fisher, Oriana S., primary, Liu, Weizhi, additional, Zhang, Rong, additional, Stiegler, Amy L., additional, Ghedia, Sondhya, additional, Weber, James L., additional, and Boggon, Titus J., additional
- Published
- 2015
- Full Text
- View/download PDF
15. Mammalian Mitochondrial and Cytosolic Folylpolyglutamate Synthetase Maintain the Subcellular Compartmentalization of Folates
- Author
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Lawrence, Scott A., primary, Titus, Steven A., additional, Ferguson, Jennifer, additional, Heineman, Amy L., additional, Taylor, Shirley M., additional, and Moran, Richard G., additional
- Published
- 2014
- Full Text
- View/download PDF
16. Structural Determinants for Binding of Sorting Nexin 17 (SNX17) to the Cytoplasmic Adaptor Protein Krev Interaction Trapped 1 (KRIT1)
- Author
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Stiegler, Amy L., primary, Zhang, Rong, additional, Liu, Weizhi, additional, and Boggon, Titus J., additional
- Published
- 2014
- Full Text
- View/download PDF
17. Extracellular cathepsin Z signals through the α 5 integrin and augments NLRP3 inflammasome activation.
- Author
-
Campden RI, Warren AL, Greene CJ, Chiriboga JA, Arnold CR, Aggarwal D, McKenna N, Sandall CF, MacDonald JA, and Yates RM
- Subjects
- Animals, Inflammation metabolism, Integrin alpha5 metabolism, Interleukin-1beta metabolism, Mice, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Silicon Dioxide pharmacology, Silicosis metabolism, Cathepsin Z metabolism, Inflammasomes metabolism
- Abstract
Respiratory silicosis is a preventable occupational disease that develops secondary to the aspiration of crystalline silicon dioxide (silica) into the lungs, activation of the NLRP3 inflammasome, and IL-1β production. Cathepsin Z has been associated with the development of inflammation and IL-1β production; however, the mechanism of how cathepsin Z leads to IL-1β production is unknown. Here, the requirement for cathepsin Z in silicosis was determined using WT mice and mice deficient in cathepsin Z. The activation of the NLRP3 inflammasome in macrophages was studied using WT and cathepsin Z-deficient bone marrow-derived murine dendritic cells and the human monocytic cell line THP-1. The cells were activated with silica, and IL-1β release was determined using enzyme-linked immunosorbent assay or IL-1β bioassays. The relative contribution of the active domain or integrin-binding domain of cathepsin Z was studied using recombinant cathepsin Z constructs and the α
5 integrin neutralizing antibody. We report that the lysosomal cysteine protease cathepsin Z potentiates the development of inflammation associated with respiratory silicosis by augmenting NLRP3 inflammasome-derived IL-1β expression in response to silica. The secreted cathepsin Z functions nonproteolytically via the internal integrin-binding domain to impact caspase-1 activation and the production of active IL-1β through integrin α5 without affecting the transcription levels of NLRP3 inflammasome components. This work reveals a regulatory pathway for the NLRP3 inflammasome that occurs in an outside-in fashion and provides a link between extracellular cathepsin Z and inflammation. Furthermore, it reveals a level of NLRP3 inflammasome regulation that has previously only been found downstream of extracellular pathogens., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
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