C M Overall

Summary

Affiliation: University of British Columbia
Country: Canada

Publications

  1. pmc Bone sialoprotein does not interact with pro-gelatinase A (MMP-2) or mediate MMP-2 activation
    Queena Hwang
    CIHR Group in Matrix Dynamics, University of Toronto, Toronto, Canada
    BMC Cancer 9:121. 2009
  2. pmc Dilating the degradome: matrix metalloproteinase 2 (MMP-2) cuts to the heart of the matter
    Christopher M Overall
    The UBC Centre for Blood Research, CIHR Group in Matrix Dynamics, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    Biochem J 383:e5-7. 2004
  3. ncbi Domain interactions in the gelatinase A.TIMP-2.MT1-MMP activation complex. The ectodomain of the 44-kDa form of membrane type-1 matrix metalloproteinase does not modulate gelatinase A activation
    C M Overall
    Department of Oral Biological and Medical Sciences and the Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 275:39497-506. 2000
  4. ncbi Molecular determinants of metalloproteinase substrate specificity: matrix metalloproteinase substrate binding domains, modules, and exosites
    Christopher M Overall
    University of British Columbia, Vancouver, Canada
    Mol Biotechnol 22:51-86. 2002
  5. ncbi Degradomics: systems biology of the protease web. Pleiotropic roles of MMPs in cancer
    Christopher M Overall
    The UBC Centre for Blood Research, Life Sciences Institute, CBCRA Program in Breast Cancer Metastasis, Department of Oral Biological, University of British Columbia, Vancouver, B C, Canada, V6T 1Z3
    Cancer Metastasis Rev 25:69-75. 2006
  6. pmc Towards third generation matrix metalloproteinase inhibitors for cancer therapy
    C M Overall
    CBCRA Program in Breast Cancer Metastasis, Department of Oral Biological and Medical Sciences, The UBC Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Br J Cancer 94:941-6. 2006
  7. ncbi Protease degradomics: mass spectrometry discovery of protease substrates and the CLIP-CHIP, a dedicated DNA microarray of all human proteases and inhibitors
    Christopher M Overall
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    Biol Chem 385:493-504. 2004
  8. ncbi Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy
    Christopher M Overall
    University of British Columbia Centre for Blood Research, CBCRA Program in Breast Cancer Metastasis, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    Nat Rev Cancer 6:227-39. 2006
  9. doi Proteomic identification of multitasking proteins in unexpected locations complicates drug targeting
    Georgina S Butler
    Centre for Blood Research, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, VT6 1Z3, Canada
    Nat Rev Drug Discov 8:935-48. 2009
  10. ncbi Cellular activation of MMP-2 (gelatinase A) by MT2-MMP occurs via a TIMP-2-independent pathway
    C J Morrison
    Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 276:47402-10. 2001

Collaborators

Detail Information

Publications79

  1. pmc Bone sialoprotein does not interact with pro-gelatinase A (MMP-2) or mediate MMP-2 activation
    Queena Hwang
    CIHR Group in Matrix Dynamics, University of Toronto, Toronto, Canada
    BMC Cancer 9:121. 2009
    ..This model is particularly relevant to cancer cell metastasis to bone since BSP, bound to the alphavbeta3 integrin through its arginine-glycine-aspartic acid motif, could recruit MMP-2 to the cell surface...
  2. pmc Dilating the degradome: matrix metalloproteinase 2 (MMP-2) cuts to the heart of the matter
    Christopher M Overall
    The UBC Centre for Blood Research, CIHR Group in Matrix Dynamics, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    Biochem J 383:e5-7. 2004
    ....
  3. ncbi Domain interactions in the gelatinase A.TIMP-2.MT1-MMP activation complex. The ectodomain of the 44-kDa form of membrane type-1 matrix metalloproteinase does not modulate gelatinase A activation
    C M Overall
    Department of Oral Biological and Medical Sciences and the Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 275:39497-506. 2000
    ..Hence, the ectodomain of the remnant 44-kDa form of MT1-MMP appears to play little if any role in the activation of gelatinase A favoring the hypothesis that it accumulates on the cell surface as an inactive, stable degradation product...
  4. ncbi Molecular determinants of metalloproteinase substrate specificity: matrix metalloproteinase substrate binding domains, modules, and exosites
    Christopher M Overall
    University of British Columbia, Vancouver, Canada
    Mol Biotechnol 22:51-86. 2002
    ....
  5. ncbi Degradomics: systems biology of the protease web. Pleiotropic roles of MMPs in cancer
    Christopher M Overall
    The UBC Centre for Blood Research, Life Sciences Institute, CBCRA Program in Breast Cancer Metastasis, Department of Oral Biological, University of British Columbia, Vancouver, B C, Canada, V6T 1Z3
    Cancer Metastasis Rev 25:69-75. 2006
    ..These sophisticated cellular control functions highlight new intervention points in multiple pathways to treat early stage cancer...
  6. pmc Towards third generation matrix metalloproteinase inhibitors for cancer therapy
    C M Overall
    CBCRA Program in Breast Cancer Metastasis, Department of Oral Biological and Medical Sciences, The UBC Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Br J Cancer 94:941-6. 2006
    ..We explore how MMP inhibitor drugs might be developed to achieve potent selectivity for validated MMP targets yet therapeutically spare MMP antitargets that are critical in host protection...
  7. ncbi Protease degradomics: mass spectrometry discovery of protease substrates and the CLIP-CHIP, a dedicated DNA microarray of all human proteases and inhibitors
    Christopher M Overall
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    Biol Chem 385:493-504. 2004
    ....
  8. ncbi Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy
    Christopher M Overall
    University of British Columbia Centre for Blood Research, CBCRA Program in Breast Cancer Metastasis, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    Nat Rev Cancer 6:227-39. 2006
    ..These effects might partially account for the failure of MMP inhibitors in clinical trials. What are the major challenges in MMP target validation and MMP-inhibitor-drug development?..
  9. doi Proteomic identification of multitasking proteins in unexpected locations complicates drug targeting
    Georgina S Butler
    Centre for Blood Research, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, VT6 1Z3, Canada
    Nat Rev Drug Discov 8:935-48. 2009
    ..Given a fair chance, proteomics could reveal novel and unforeseen biology with important ramifications for target validation in drug discovery...
  10. ncbi Cellular activation of MMP-2 (gelatinase A) by MT2-MMP occurs via a TIMP-2-independent pathway
    C J Morrison
    Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 276:47402-10. 2001
    ....
  11. ncbi Tissue inhibitor of metalloproteinases-4 inhibits but does not support the activation of gelatinase A via efficient inhibition of membrane type 1-matrix metalloproteinase
    H F Bigg
    Faculty of Dentistry and Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Cancer Res 61:3610-8. 2001
    ..Hence, TIMP-4 regulates gelatinase A activity by efficient inhibition of MT1-MMP-mediated activation and by inhibiting the activated enzyme and, thus, is a tumor resistance factor in the peritumor stroma...
  12. ncbi Subsite mapping of the human pancreatic alpha-amylase active site through structural, kinetic, and mutagenesis techniques
    G D Brayer
    Department of Biochemistry, University of British Columbia, Vancouver V6T 1Z3, Canada
    Biochemistry 39:4778-91. 2000
    ..Structural analyses of the Asp300Asn variant of human pancreatic alpha-amylase and its complex with acarbose clearly demonstrate the importance of Asp300 to the mode of inhibitor binding...
  13. ncbi Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3
    G A McQuibban
    Department of Biochemistry and Molecular Biology, Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
    Science 289:1202-6. 2000
    ..This suggests that matrix metalloproteinases are both effectors and regulators of the inflammatory response...
  14. ncbi Proteomic validation of protease drug targets: pharmacoproteomics of matrix metalloproteinase inhibitor drugs using isotope-coded affinity tag labelling and tandem mass spectrometry
    G S Butler
    Centre for Blood Research, Life Sciences Institute, University of British Columbia, Vancouver, V6T 1Z3, Canada
    Curr Pharm Des 13:263-70. 2007
    ....
  15. ncbi Identification of the tissue inhibitor of metalloproteinases-2 (TIMP-2) binding site on the hemopexin carboxyl domain of human gelatinase A by site-directed mutagenesis. The hierarchical role in binding TIMP-2 of the unique cationic clusters of hemopexin
    C M Overall
    Faculty of Dentistry and the Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 274:4421-9. 1999
    ..This location implies that considerable molecular movement of the TIMP-2. C domain complex would be needed for the bound TIMP-2 to inhibit in cis the gelatinase A active site...
  16. ncbi Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1
    G A McQuibban
    Department of Biochemistry and Molecular Biology, Oral Biological and Medical Sciences, Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 276:43503-8. 2001
    ..These data suggest that MMPs may be important regulatory proteases in attenuating SDF-1 function and point to a deep convergence of two important networks, chemokines and MMPs, to regulate leukocytic activity in vivo...
  17. ncbi Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human gelatinase A. TIMP-4 binds progelatinase A and the COOH-terminal domain in a similar manner to TIMP-2
    H F Bigg
    Faculty of Dentistry and Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 272:15496-500. 1997
    ..This new phenomenon may be of important physiological significance in modulating the cell surface activation of progelatinase A...
  18. pmc Pharmacoproteomics of a metalloproteinase hydroxamate inhibitor in breast cancer cells: dynamics of membrane type 1 matrix metalloproteinase-mediated membrane protein shedding
    Georgina S Butler
    Department of Oral Biological and Medical Sciences, Centre for Blood Research, University of British Columbia, Vancouver, Canada
    Mol Cell Biol 28:4896-914. 2008
    ..Hence, this approach describes the dynamic pattern of cell membrane ectodomain shedding and its perturbation upon metalloproteinase drug treatment...
  19. pmc Evidence for polymorphonuclear leukocyte collagenase and 92-kilodalton gelatinase in gingival crevicular fluid
    C M Overall
    Faculty of Dentistry, University of British Columbia, Vancouver, Canada
    Infect Immun 59:4687-92. 1991
    ....
  20. doi Membrane protease degradomics: proteomic identification and quantification of cell surface protease substrates
    Georgina S Butler
    Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
    Methods Mol Biol 528:159-76. 2009
    ..g. vector or inactive protease) and differential labelling, shed proteins can be identified and quantified by mass spectrometry (MS), MS/MS fragmentation and database searching...
  21. pmc Cloning, mutagenesis, and structural analysis of human pancreatic alpha-amylase expressed in Pichia pastoris
    E H Rydberg
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada
    Protein Sci 8:635-43. 1999
    ..The decreased k(cat)/Km values for the mutants confirm that D197 plays a crucial role in the hydrolytic activity of HPA, presumably as the catalytic nucleophile...
  22. pmc A statistics-based platform for quantitative N-terminome analysis and identification of protease cleavage products
    Ulrich auf dem Keller
    Department of Biochemistry and Molecular Biology, Centre for Blood Research, University of British Columbia, 4 401 Life Sciences Institute, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada
    Mol Cell Proteomics 9:912-27. 2010
    ....
  23. pmc Identification of candidate angiogenic inhibitors processed by matrix metalloproteinase 2 (MMP-2) in cell-based proteomic screens: disruption of vascular endothelial growth factor (VEGF)/heparin affin regulatory peptide (pleiotrophin) and VEGF/Connective
    Richard A Dean
    University of British Columbia, Centre for Blood Research, 4 401 Life Sciences Institute, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3
    Mol Cell Biol 27:8454-65. 2007
    ..Hence the unmasking of cytokines, such as VEGF, by metalloproteinase processing of their binding proteins is a new mechanism in the control of cytokine activation and angiogenesis...
  24. ncbi Proteomic discovery of protease substrates
    Oliver Schilling
    The UBC Centre for Blood Research, Departments of Oral Biological and Medical Sciences, and Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada
    Curr Opin Chem Biol 11:36-45. 2007
    ..Together with activity-based probes for the profiling of functional proteases, there is now in place an array of complementary technologies to dissect the 'protease web' and its distortion in pathology...
  25. doi Novel matrix metalloproteinase inhibitor [18F]marimastat-aryltrifluoroborate as a probe for in vivo positron emission tomography imaging in cancer
    Ulrich auf dem Keller
    UBC Centre for Blood Research, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
    Cancer Res 70:7562-9. 2010
    ..The labeled drug cleared primarily via the hepatobiliary and gastrointestinal tract, with multiple animals imaged in independent experiments, confirming the ease of this new labeling strategy...
  26. doi Cell-based identification of natural substrates and cleavage sites for extracellular proteases by SILAC proteomics
    Magda Gioia
    Department of Oral Biological and Medical Sciences, Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
    Methods Mol Biol 539:131-53. 2009
    ..Using proteomes exposed or not to a particular protease enables biologically relevant substrates and their cleavage sites to be identified and quantified by tandem mass spectrometry proteomics and database searching...
  27. doi Matrix metalloproteinases: what do they not do? New substrates and biological roles identified by murine models and proteomics
    David Rodriguez
    Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    Biochim Biophys Acta 1803:39-54. 2010
    ....
  28. doi Identification of cellular MMP substrates using quantitative proteomics: isotope-coded affinity tags (ICAT) and isobaric tags for relative and absolute quantification (iTRAQ)
    Georgina S Butler
    Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
    Methods Mol Biol 622:451-70. 2010
    ..Thus proteins present in altered amounts between protease-expressing and null cells are implicated as protease substrates and can be further validated as such...
  29. doi Matrix metalloproteinase proteomics: substrates, targets, and therapy
    Charlotte J Morrison
    Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
    Curr Opin Cell Biol 21:645-53. 2009
    ..Since MMPs do not operate alone but are part of the 'protease web', it is necessary to use system-wide approaches to understand MMP proteolysis in vivo, to discover new biological roles and their potential for therapeutic modification...
  30. ncbi Characterization of the distinct collagen binding, helicase and cleavage mechanisms of matrix metalloproteinase 2 and 14 (gelatinase A and MT1-MMP): the differential roles of the MMP hemopexin c domains and the MMP-2 fibronectin type II modules in collage
    Eric M Tam
    Department of Biochemistry, UBC Centre for Blood Research and the Canadian Institutes for Health Research Group in Matrix Dynamics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 279:43336-44. 2004
    ..Hence, the MMP family has evolved two distinct mechanisms for collagen triple helicase activity using two structurally distinct domains, with triple helicase activity occurring independent of alpha-chain hydrolysis...
  31. pmc Membrane protease proteomics: Isotope-coded affinity tag MS identification of undescribed MT1-matrix metalloproteinase substrates
    Eric M Tam
    Department of Biochemistry and Molecular Biology, Centre for Blood Research and Canadian Institutes of Health Research Group in Matrix Dynamics, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Proc Natl Acad Sci U S A 101:6917-22. 2004
    ....
  32. ncbi Discovery of chemokine substrates for matrix metalloproteinases by exosite scanning: a new tool for degradomics
    Christopher M Overall
    Department of Biochemistry and Molecular Biology, University of British Columiba, Vancouver, Canada
    Biol Chem 383:1059-66. 2002
    ..Hence, bioinformatic searches for protease substrates based on scissile bond preference will only reveal a subset of substrates unless the influence of exosites is considered...
  33. ncbi The canonical methionine 392 of matrix metalloproteinase 2 (gelatinase A) is not required for catalytic efficiency or structural integrity: probing the role of the methionine-turn in the metzincin metalloprotease superfamily
    Georgina S Butler
    Departments of Oral Biological and Medical Sciences and Biochemistry and Molecular Biology, Center for Blood Research, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 279:15615-20. 2004
    ..These results challenge the dogma that this methionine residue and the Met-turn, which are absolutely conserved in all of the subfamilies of the metzincins, play an essential role in catalysis or active site structure...
  34. doi Proteome-derived, database-searchable peptide libraries for identifying protease cleavage sites
    Oliver Schilling
    The UBC Centre for Blood Research, Department of Oral Biological and Medical Sciences, 4 401 Life Sciences Institute, 2350 Health Sciences Mall, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    Nat Biotechnol 26:685-94. 2008
    ..Profiling of HIV protease 1, caspase 3, caspase 7, cathepsins K and G, elastase and thrombin showed that this approach is broadly applicable to all mechanistic classes of endoproteases...
  35. ncbi Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo
    G Angus McQuibban
    Department of Biochemistry and Molecular Biology and the Biomedical Research Centre, University of British Columbia, Vancouver, Canada
    Blood 100:1160-7. 2002
    ..We propose that MMPs have an important role in modulating inflammatory and immune responses by processing chemokines in wound healing and in disease...
  36. doi Isotopic labeling of terminal amines in complex samples identifies protein N-termini and protease cleavage products
    Oded Kleifeld
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
    Nat Biotechnol 28:281-8. 2010
    ....
  37. ncbi In search of partners: linking extracellular proteases to substrates
    Christopher M Overall
    The UBC Centre for Blood Research, CBCRA Program in Breast Cancer Metastasis, Department of Oral Biological and Medical Sciences, University of British Columbia, 4 401 Life Sciences Center, Vancouver, British Columbia, V6T 1Z3, Canada
    Nat Rev Mol Cell Biol 8:245-57. 2007
    ..Elucidating the substrate degradomes of proteases will help us to understand the function of proteases in development and disease and to validate proteases as drug targets...
  38. pmc Multiplex N-terminome analysis of MMP-2 and MMP-9 substrate degradomes by iTRAQ-TAILS quantitative proteomics
    Anna Prudova
    Department of Biochemistry and Molecular Biology, Centre for Blood Research, University of British Columbia, 4 401 Life Sciences Institute, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada
    Mol Cell Proteomics 9:894-911. 2010
    ..Hence, N-terminomics analyses using iTRAQ-TAILS links gelatinases with new mechanisms of action in angiogenesis and reveals unpredicted restrictions in substrate repertoires for these two very similar proteases...
  39. ncbi Proteomics discovery of metalloproteinase substrates in the cellular context by iTRAQ labeling reveals a diverse MMP-2 substrate degradome
    Richard A Dean
    Department of Oral Biological and Medical Sciences, 4 401 Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada
    Mol Cell Proteomics 6:611-23. 2007
    ..Hence this advance in degradomics cell-based screens for native protein substrates casts new light on the roles for proteases in cell function...
  40. ncbi TIMP independence of matrix metalloproteinase (MMP)-2 activation by membrane type 2 (MT2)-MMP is determined by contributions of both the MT2-MMP catalytic and hemopexin C domains
    Charlotte J Morrison
    Centre for Blood Research and Department of Oral Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 281:26528-39. 2006
    ..In tissues or pathologies characterized by low TIMP-2 expression, this pathway may represent an alternative means of rapidly generating low levels of active MMP-2...
  41. doi Protease proteomics: revealing protease in vivo functions using systems biology approaches
    Alain Doucet
    University of British Columbia, Centre for Blood Research, 4 401 Life Sciences Institute, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3
    Mol Aspects Med 29:339-58. 2008
    ..This will indicate which proteases participate in defined pathologies and will help targeting specific proteases for disease treatments...
  42. ncbi Mannose-binding lectin (MBL) mutants are susceptible to matrix metalloproteinase proteolysis: potential role in human MBL deficiency
    Georgina S Butler
    Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 277:17511-9. 2002
    ..MMPs are likely to contribute to MBL deficiency in individuals with variant alleles and may also be involved in clearance of MBL and modulation of the host response in normal individuals...
  43. ncbi Collagen binding properties of the membrane type-1 matrix metalloproteinase (MT1-MMP) hemopexin C domain. The ectodomain of the 44-kDa autocatalytic product of MT1-MMP inhibits cell invasion by disrupting native type I collagen cleavage
    Eric M Tam
    C I H R Group in Matrix Dynamics, Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 277:39005-14. 2002
    ....
  44. doi Epithelial-mesenchymal transition (EMT) is not sufficient for spontaneous murine breast cancer metastasis
    Yuanmei Lou
    Department of Cancer Genetics, BC Cancer Research Centre, University of British Columbia, Vancouver, BC, Canada
    Dev Dyn 237:2755-68. 2008
    ..Gene expression analysis of primary tumors did not identify differences in EMT markers, but did reveal candidate genes that may influence metastatic ability...
  45. doi Metadegradomics: toward in vivo quantitative degradomics of proteolytic post-translational modifications of the cancer proteome
    Alain Doucet
    Centre for Blood Research, 4 401 Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada
    Mol Cell Proteomics 7:1925-51. 2008
    ..At the global level, the N terminome analysis of whole communities of proteases in tissues and organs in vivo provides a full scale understanding of the protease web and the web-sculpted proteome, so defining metadegradomics...
  46. doi Updated biological roles for matrix metalloproteinases and new "intracellular" substrates revealed by degradomics
    Georgina S Butler
    Centre for Blood Research, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, BC, Canada
    Biochemistry 48:10830-45. 2009
    ..Here we review progress made in the field of degradomics and present a current view of the MMP degradome...
  47. ncbi Proteomic identification of cellular protease substrates using isobaric tags for relative and absolute quantification (iTRAQ)
    Richard A Dean
    University of British Columbia, Vancouver, British Columbia, Canada
    Curr Protoc Protein Sci . 2007
    ..This signature ion peak identifies the peptides originating from the protease-transfected or control cells; comparison of the peak areas enables relative quantitation of the peptide between the samples...
  48. ncbi Mechanistic analyses of catalysis in human pancreatic alpha-amylase: detailed kinetic and structural studies of mutants of three conserved carboxylic acids
    Edwin H Rydberg
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
    Biochemistry 41:4492-502. 2002
    ..This may also suggest that D300 plays a crucial role in enzymic interactions with the nucleophilic water during the hydrolysis of the glycosidic bond...
  49. ncbi In situ extension as an approach for identifying novel alpha-amylase inhibitors
    Shin Numao
    Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada
    J Biol Chem 279:48282-91. 2004
    ..This approach to the discovery and structural analysis of amylase inhibitors should be generally applicable to other endoglucosidases and readily adaptable to a high throughput format...
  50. doi Chapter 13. Characterizing proteolytic processing of chemokines by mass spectrometry, biochemistry, neo-epitope antibodies and functional assays
    Amanda E Starr
    Department of Biochemistry, University of British Columbia, Centre for Blood Research, Life Sciences Institute, Vancouver, British Columbia, Canada
    Methods Enzymol 461:281-307. 2009
    ..Herein we provide techniques to assess, detect, and characterize protease activity on chemokines and the biologic outcomes...
  51. pmc Structural and mechanistic studies of chloride induced activation of human pancreatic alpha-amylase
    Robert Maurus
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Protein Sci 14:743-55. 2005
    ....
  52. ncbi Utilization of a novel recombinant myoglobin fusion protein expression system to characterize the tissue inhibitor of metalloproteinase (TIMP)-4 and TIMP-2 C-terminal domain and tails by mutagenesis. The importance of acidic residues in binding the MMP-2
    Heidi S T Kai
    Canadian Institute of Health Research Group in Matrix Dynamics and the Department of Oral Biological and Medical Sciences, Faculty of Dentistry, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 277:48696-707. 2002
    ....
  53. doi Toward [18F]-labeled aryltrifluoroborate radiotracers: in vivo positron emission tomography imaging of stable aryltrifluoroborate clearance in mice
    Richard Ting
    Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, B C V6T 1Z1, Canada
    J Am Chem Soc 130:12045-55. 2008
    ..This work validates initial claims that boronic esters are potentially useful as readily labeled precursors to [(18)F]-PET reagents...
  54. doi Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+ CXC chemokines and generates CCL2, -7, -8, and -13 antagonists: potential role of the macrophage in terminating polymorphonuclear leukocyte influx
    Richard A Dean
    Departments ofOral Biological and Medical Sciences, Centre for Blood Research, University of British Columbia, Vancouver, Canada
    Blood 112:3455-64. 2008
    ..We propose that the macrophage, specifically through MMP-12, assists in orchestrating the regulation of acute inflammatory responses by precise proteolysis of ELR(+)CXC and CC chemokines...
  55. doi Matrix metalloproteinase processing of CXCL11/I-TAC results in loss of chemoattractant activity and altered glycosaminoglycan binding
    Jennifer H Cox
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 283:19389-99. 2008
    ..Hence, these results reveal potential new roles in down-regulating Th1 lymphocyte chemoattraction through MMP processing of CXCL11...
  56. ncbi Cortactin associates with N-cadherin adhesions and mediates intercellular adhesion strengthening in fibroblasts
    Tarek Y El Sayegh
    CIHR Group in Matrix Dynamics, University of Toronto, Fitzgerald Building, 150 College Street, Ontario, M5S 3E2, Canada
    J Cell Sci 117:5117-31. 2004
    ..Thus cortactin, and phosphorylation of its tyrosine residues, are important for N-cadherin-mediated intercellular adhesion strength...
  57. doi Activated caspase-6 and caspase-6-cleaved fragments of huntingtin specifically colocalize in the nucleus
    Simon C Warby
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, 980 West 28th Avenue, Vancouver, British Columbia, Canada
    Hum Mol Genet 17:2390-404. 2008
    ..The different cellular itineraries of endogenously generated caspase products of huntingtin may provide an explanation for the selective toxicity of huntingtin fragments cleaved at amino acid 586...
  58. ncbi Probing the role of the chloride ion in the mechanism of human pancreatic alpha-amylase
    Shin Numao
    Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z1
    Biochemistry 41:215-25. 2002
    ..We propose that the chloride is required to increase the pK(a) of the acid/base catalyst, E233, which would otherwise be lower due to the presence of R337, a positively charged residue...
  59. ncbi Pivotal molecular determinants of peptidic and collagen triple helicase activities reside in the S3' subsite of matrix metalloproteinase 8 (MMP-8): the role of hydrogen bonding potential of ASN188 and TYR189 and the connecting cis bond
    Gayle R Pelman
    University of British Columbia Centre for Blood Research and the Canadian Institutes for Health Research Group in Matrix Dynamics, University of British Columbia, Vancouver, Canada
    J Biol Chem 280:2370-7. 2005
    ....
  60. ncbi Protease research in the era of systems biology
    Ulrich auf dem Keller
    The UBC Centre for Blood Research, Department of Oral Biological and Medical Sciences, and Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
    Biol Chem 388:1159-62. 2007
    ..Understanding the protease web and its perturbations in pathology will help to develop new therapeutics for the treatment of diseases, such as cancer, arthritis and chronic obstructive pulmonary diseases...
  61. doi Analysis of the degradome with the CLIP-CHIP microarray
    Reinhild Kappelhoff
    Department of Oral Biological and Medical Sciences, Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
    Methods Mol Biol 622:175-93. 2010
    ....
  62. ncbi Function of liver activation-regulated chemokine/CC chemokine ligand 20 is differently affected by cathepsin B and cathepsin D processing
    Lara Hasan
    Institute of Pathology, University of Bern, Bern, Switzerland
    J Immunol 176:6512-22. 2006
    ..Thus, we propose a model where cathepsin D inactivates CCL20 and possibly prevents the establishment of an effective antitumoral immune response in melanomas...
  63. doi Stromal cell-derived factors 1alpha and 1beta, inflammatory protein-10 and interferon-inducible T cell chemo-attractant are novel substrates of dipeptidyl peptidase 8
    Katerina Ajami
    Centenary Institute, Faculty of Medicine, University of Sydney, Newtown, Sydney, NSW, Australia
    FEBS Lett 582:819-25. 2008
    ..This has implications for DP8 substrate specificity. Chemokine cleavage and inactivation may occur in vivo upon cell lysis and release of DP8 or in the inactivation of internalized chemokine/receptor complexes...
  64. ncbi Dissecting the role of matrix metalloproteinases (MMP) and integrin alpha(v)beta3 in angiogenesis in vitro: absence of hemopexin C domain bioactivity, but membrane-Type 1-MMP and alpha(v)beta3 are critical
    Riccardo E Nisato
    Department of Morphology, University Medical Center, Geneva, Switzerland
    Cancer Res 65:9377-87. 2005
    ....
  65. pmc Cell surface chondroitin sulfate glycosaminoglycan in melanoma: role in the activation of pro-MMP-2 (pro-gelatinase A)
    Joji Iida
    Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
    Biochem J 403:553-63. 2007
    ..These results suggest that C4S, which is expressed on tumour cell surface, can function to bind to pro-MMP-2 and facilitate its activation by MT3-MMP-expressing tumour cells to enhance invasion and metastasis...
  66. ncbi Cancer cell-associated fibronectin induces release of matrix metalloproteinase-2 from normal fibroblasts
    Sonia Saad
    Westmead Institute for Cancer Research, Westmead Millennium Institute, Department of Medicine, University of Sydney, Australia
    Cancer Res 62:283-9. 2002
    ..Because an identical mechanism can be demonstrated using fibroblasts from different sources, it is likely to be important for the rapid movement of malignant cells into a variety of normal tissues...
  67. ncbi Regulation of intercellular adhesion strength in fibroblasts
    Matthew W C Chan
    Canadian Institutes of Health Research CIHR Group in Matrix Dynamics, Faculty of Dentistry, University of Toronto, Toronto, Ontario M5S 3E2, Canada
    J Biol Chem 279:41047-57. 2004
    ..These data indicate that increased actin barbed end generation by the severing activity of gelsolin associated with N-cadherin regulates intercellular adhesion strength...
  68. ncbi The roles of substrate thermal stability and P2 and P1' subsite identity on matrix metalloproteinase triple-helical peptidase activity and collagen specificity
    Dmitriy Minond
    Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431 0991, USA
    J Biol Chem 281:38302-13. 2006
    ..Further exploration of MMP active sites and exosites, in combination with substrate conformation, may prove valuable for additional dissection of collagenolysis and yield information useful in the design of more selective MMP inhibitors...
  69. ncbi Proteolytic host cell enzymes in gingival crevice fluid
    Veli Jukka Uitto
    Periodontol 2000 31:77-104. 2003
  70. pmc The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases
    Nadia Nour
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    Mol Biol Cell 16:5215-26. 2005
    ..In conclusion, the CRD of PC5A and PACE4 functions as a cell surface anchor favoring the processing of their cognate surface-anchored substrates, including endothelial lipase...
  71. ncbi Protease degradomics: a new challenge for proteomics
    Carlos Lopez-Otin
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nat Rev Mol Cell Biol 3:509-19. 2002
  72. pmc Matrix metalloproteinase-8 facilitates neutrophil migration through the corneal stromal matrix by collagen degradation and production of the chemotactic peptide Pro-Gly-Pro
    Michelle Lin
    Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106 7286, USA
    Am J Pathol 173:144-53. 2008
    ....
  73. pmc Identification, regulation and role of tissue inhibitor of metalloproteinases-4 (TIMP-4) in human platelets
    Anna Radomski
    Department of Pharmacology, University of Alberta, 9 50 Medical Sciences Building, Edmonton, Ontario, Canada T6G 2H7
    Br J Pharmacol 137:1330-8. 2002
    ..11. Human rTIMP-4 exerted a biphasic effect on HT-1080 cells-induced aggregation. 12. Thus, TIMP-4 is the major intraplatelet MMP inhibitor and it is involved in regulation of platelet aggregation and recruitment...
  74. doi Collagenase-2 deficiency or inhibition impairs experimental autoimmune encephalomyelitis in mice
    Alicia R Folgueras
    Departamento de Bioquimica y Biologia Molecular, and Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, and Servicio de Anatomía Patológica, Hospital Central de Asturias, Oviedo 33006, Spain
    J Biol Chem 283:9465-74. 2008
    ..Based on these findings, we conclude that MMP-8 plays an important role in EAE development and propose that this enzyme may be a novel therapeutic target in human neuro-inflammatory diseases such as multiple sclerosis...
  75. ncbi Protease yoga: extreme flexibility of a matrix metalloproteinase
    Christopher M Overall
    Structure 15:1159-61. 2007
  76. ncbi Plant collagenase: unique collagenolytic activity of cysteine proteases from ginger
    Misook Kim
    School of Molecular and Microbial Sciences, The University of Queensland, St Lucia, Australia
    Biochim Biophys Acta 1770:1627-35. 2007
    ..The results support a role for ginger proteases as an alternative to papain, in commercial applications such as meat tenderization, where collagen is the target substrate...
  77. pmc Differentiation of secreted and membrane-type matrix metalloproteinase activities based on substitutions and interruptions of triple-helical sequences
    Dmitriy Minond
    Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, Florida 33431 0991, USA
    Biochemistry 46:3724-33. 2007
    ..Such differences may be significant for understanding MMP mechanisms of action and aid in the development of selective MMP inhibitors...
  78. ncbi HIV-induced metalloproteinase processing of the chemokine stromal cell derived factor-1 causes neurodegeneration
    Kunyan Zhang
    Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada
    Nat Neurosci 6:1064-71. 2003
    ..Hence, this study identifies a new in vivo neurotoxic pathway in which cleavage of a chemokine by an induced metalloproteinase results in neuronal apoptosis that leads to neurodegeneration...
  79. pmc A critical role for the membrane-type 1 matrix metalloproteinase in collagen phagocytosis
    Hyejin Lee
    Canadian Institutes of Health Research Group in Matrix Dynamics, Faculty of Dentistry, and Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 3E2, Canada
    Mol Biol Cell 17:4812-26. 2006
    ..In contrast to MT1-MMP, the gelatinolytic activity of MMP-2 was not required for collagen phagocytosis. These studies demonstrate a pivotal role of catalytically active MT1-MMP in preparing collagen fibrils for phagocytic degradation...