| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 16, 12501-12504, April 20, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
§,
From the The proteoglycan aggrecan is an important
major component of cartilage matrix that gives articular cartilage the
ability to withstand compression. Increased breakdown of aggrecan is
associated with the development of arthritis and is considered to be
catalyzed by aggrecanases, members of the ADAM-TS family of
metalloproteinases. Four endogenous tissue inhibitors of
metalloproteinases (TIMPs) regulate the activities of functional matrix
metalloproteinases (MMPs), enzymes that degrade most components of
connective tissue, but no endogenous factors responsible for the
regulation of aggrecanases have been found. We show here that the
N-terminal inhibitory domain of TIMP-3, a member of the TIMP family
that has functional properties distinct from other TIMPs, is a strong
inhibitor of human aggrecanases 1 and 2, with Ki
values in the subnanomolar range. This truncated inhibitor, which lacks
the C-terminal domain that is responsible for interactions with
molecules other than active metalloproteinases, is produced at high
yield by bacterial expression and folding from inclusion bodies.
This provides a starting point for developing a biologically
available aggrecanase inhibitor suitable for the treatment of arthritis.
Department of Biochemistry and Molecular
Biology, University of Miami School of Medicine, Miami, Florida 33101 and the § Kennedy Institute of Rheumatology, Imperial
College School of Medicine, 1 Aspenlea Road, Hammersmith, London W6 8LH
United Kingdom
This article has been cited by other articles:
|
|
 |
|
  S. Higashi and K. Miyazaki Identification of Amino Acid Residues of the Matrix Metalloproteinase-2 Essential for Its Selective Inhibition by {beta}-Amyloid Precursor Protein-derived Inhibitor J. Biol. Chem., April 11, 2008; 283(15): 10068 - 10078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fushimi, L. Troeberg, H. Nakamura, N. H. Lim, and H. Nagase Functional Differences of the Catalytic and Non-catalytic Domains in Human ADAMTS-4 and ADAMTS-5 in Aggrecanolytic Activity J. Biol. Chem., March 14, 2008; 283(11): 6706 - 6716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-S. Shieh, K. J. Mathis, J. M. Williams, R. L. Hills, J. F. Wiese, T. E. Benson, J. R. Kiefer, M. H. Marino, J. N. Carroll, J. W. Leone, et al. High Resolution Crystal Structure of the Catalytic Domain of ADAMTS-5 (Aggrecanase-2) J. Biol. Chem., January 18, 2008; 283(3): 1501 - 1507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Lauer-Fields, M. Cudic, S. Wei, F. Mari, G. B. Fields, and K. Brew Engineered Sarafotoxins as Tissue Inhibitor of Metalloproteinases-like Matrix Metalloproteinase Inhibitors J. Biol. Chem., September 14, 2007; 282(37): 26948 - 26955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Hamze, S. Wei, H. Bahudhanapati, S. Kota, K. R. Acharya, and K. Brew Constraining specificity in the N-domain of tissue inhibitor of metalloproteinases-1; gelatinase-selective inhibitors Protein Sci., September 1, 2007; 16(9): 1905 - 1913. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Wayne, S.-J. Deng, A. Amour, S. Borman, R. Matico, H. L. Carter, and G. Murphy TIMP-3 Inhibition of ADAMTS-4 (Aggrecanase-1) Is Modulated by Interactions between Aggrecan and the C-terminal Domain of ADAMTS-4 J. Biol. Chem., July 20, 2007; 282(29): 20991 - 20998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. Hojilla, I. Kim, Z. Kassiri, J. E. Fata, H. Fang, and R. Khokha Metalloproteinase axes increase beta-catenin signaling in primary mouse mammary epithelial cells lacking TIMP3 J. Cell Sci., March 15, 2007; 120(6): 1050 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Lee, S. Atkinson, and G. Murphy Identification of the Extracellular Matrix (ECM) Binding Motifs of Tissue Inhibitor of Metalloproteinases (TIMP)-3 and Effective Transfer to TIMP-1 J. Biol. Chem., March 2, 2007; 282(9): 6887 - 6898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ge and D. S. Greenspan BMP1 controls TGF{beta}1 activation via cleavage of latent TGF{beta}-binding protein J. Cell Biol., October 9, 2006; 175(1): 111 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M A Majid, V A Smith, F J Matthews, A C Newby, and A D Dick Tissue inhibitor of metalloproteinase-3 differentially binds to components of Bruch's membrane Br. J. Ophthalmol., October 1, 2006; 90(10): 1310 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Haddock, A K Cross, J Plumb, J Surr, D J Buttle, R A. Bunning, and M N Woodroofe Expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS white matter Multiple Sclerosis, August 1, 2006; 12(4): 386 - 396. [Abstract] [PDF]
|
|
|
|
|
|
J. L. English, Z. Kassiri, I. Koskivirta, S. J. Atkinson, M. Di Grappa, P. D. Soloway, H. Nagase, E. Vuorio, G. Murphy, and R. Khokha Individual Timp Deficiencies Differentially Impact Pro-MMP-2 Activation J. Biol. Chem., April 14, 2006; 281(15): 10337 - 10346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-J. Oh, J. L. Martin, A. J. Williams, R. E. Peck, C. Pokorny, P. Russell, D. E. Birk, and D. J. Rhee Analysis of expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human ciliary body after latanoprost. Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 953 - 963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Will, M. Dettloff, P. Bendzko, and P. Sveshnikov A quantitative assay for aggrecanase activity. J. Biomol. Tech., December 1, 2005; 16(4): 459 - 472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. P. Langton, N. McKie, B. M. Smith, N. J. Brown, and M. D. Barker Sorsby's fundus dystrophy mutations impair turnover of TIMP-3 by retinal pigment epithelial cells Hum. Mol. Genet., December 1, 2005; 14(23): 3579 - 3586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W Hui, H E Barksby, D A Young, T E Cawston, N McKie, and A D Rowan Oncostatin M in combination with tumour necrosis factor {alpha} induces a chondrocyte membrane associated aggrecanase that is distinct from ADAMTS aggrecanase-1 or -2 Ann Rheum Dis, November 1, 2005; 64(11): 1624 - 1632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Pattoli, J. F. MacMaster, K. R. Gregor, and J. R. Burke Collagen and Aggrecan Degradation Is Blocked in Interleukin-1-Treated Cartilage Explants by an Inhibitor of I{kappa}B Kinase through Suppression of Metalloproteinase Expression J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 382 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wei, M. Kashiwagi, S. Kota, Z. Xie, H. Nagase, and K. Brew Reactive Site Mutations in Tissue Inhibitor of Metalloproteinase-3 Disrupt Inhibition of Matrix Metalloproteinases but Not Tumor Necrosis Factor-{alpha}-converting Enzyme J. Biol. Chem., September 23, 2005; 280(38): 32877 - 32882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J.R. Singh, J. C. Mason, E. A. Lidington, D. R. Edwards, R. K. Nuttall, R. Khokha, V. Knauper, G. Murphy, and J. Gavrilovic Cytokine stimulated vascular cell adhesion molecule-1 (VCAM-1) ectodomain release is regulated by TIMP-3 Cardiovasc Res, July 1, 2005; 67(1): 39 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mahmoodi, S. Sahebjam, D. Smookler, R. Khokha, and J. S. Mort Lack of Tissue Inhibitor of Metalloproteinases-3 Results in an Enhanced Inflammatory Response in Antigen-Induced Arthritis Am. J. Pathol., June 1, 2005; 166(6): 1733 - 1740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. N. Wight The ADAMTS Proteases, Extracellular Matrix, and Vascular Disease: Waking the Sleeping Giant(s)! Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 12 - 14. [Full Text] [PDF]
|
|
|
|
|
|
G. Hashimoto, M. Shimoda, and Y. Okada ADAMTS4 (Aggrecanase-1) Interaction with the C-terminal Domain of Fibronectin Inhibits Proteolysis of Aggrecan J. Biol. Chem., July 30, 2004; 279(31): 32483 - 32491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M R Hill, L Briggs, M M Montano, A Estrada, G J Laurent, M Selman, and A Pardo Promoter variants in tissue inhibitor of metalloproteinase-3 (TIMP-3) protect against susceptibility in pigeon breeders' disease Thorax, July 1, 2004; 59(7): 586 - 590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Tortorella, E. C. Arner, R. Hills, A. Easton, J. Korte-Sarfaty, K. Fok, A. J. Wittwer, R.-Q. Liu, and A.-M. Malfait {alpha}2-Macroglobulin Is a Novel Substrate for ADAMTS-4 and ADAMTS-5 and Represents an Endogenous Inhibitor of These Enzymes J. Biol. Chem., April 23, 2004; 279(17): 17554 - 17561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-L. Tsai, C.-H. Chen, C.-J. Huang, C.-M. Chou, and G.-D. Chang Purification and Cloning of an Endogenous Protein Inhibitor of Carp Nephrosin, an Astacin Metalloproteinase J. Biol. Chem., March 19, 2004; 279(12): 11146 - 11155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kashiwagi, J. J. Enghild, C. Gendron, C. Hughes, B. Caterson, Y. Itoh, and H. Nagase Altered Proteolytic Activities of ADAMTS-4 Expressed by C-terminal Processing J. Biol. Chem., March 12, 2004; 279(11): 10109 - 10119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhao, M. M. Bernardo, P. Osenkowski, A. Sohail, D. Pei, H. Nagase, M. Kashiwagi, P. D. Soloway, Y. A. DeClerck, and R. Fridman Differential Inhibition of Membrane Type 3 (MT3)-Matrix Metalloproteinase (MMP) and MT1-MMP by Tissue Inhibitor of Metalloproteinase (TIMP)-2 and TIMP-3 Regulates Pro-MMP-2 Activation J. Biol. Chem., March 5, 2004; 279(10): 8592 - 8601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Merz, R. Liu, K. Johnson, and R. Terkeltaub IL-8/CXCL8 and Growth-Related Oncogene {alpha}/CXCL1 Induce Chondrocyte Hypertrophic Differentiation J. Immunol., October 15, 2003; 171(8): 4406 - 4415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Visse and H. Nagase Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases: Structure, Function, and Biochemistry Circ. Res., May 2, 2003; 92(8): 827 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Higashi and K. Miyazaki Identification of a Region of beta -Amyloid Precursor Protein Essential for Its Gelatinase A Inhibitory Activity J. Biol. Chem., April 11, 2003; 278(16): 14020 - 14028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Collen, R. Hanemaaijer, F. Lupu, P. H. A. Quax, N. van Lent, J. Grimbergen, E. Peters, P. Koolwijk, and V. W. M. van Hinsbergh Membrane-type matrix metalloproteinase-mediated angiogenesis in a fibrin-collagen matrix Blood, March 1, 2003; 101(5): 1810 - 1817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. F. Seals and S. A. Courtneidge The ADAMs family of metalloproteases: multidomain proteins with multiple functions Genes & Dev., January 1, 2003; 17(1): 7 - 30. [Full Text] [PDF]
|
|
|
|
|
|
T. Kang, H. I. Park, Y. Suh, Y.-G. Zhao, H. Tschesche, and Q.-X. A. Sang Autolytic Processing at Glu586-Ser587 within the Cysteine-rich Domain of Human Adamalysin 19/Disintegrin-Metalloproteinase 19 Is Necessary for Its Proteolytic Activity J. Biol. Chem., December 6, 2002; 277(50): 48514 - 48522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Lee, K. Maskos, V. Knauper, P. Dodds, and G. Murphy Mapping and characterization of the functional epitopes of tissue inhibitor of metalloproteinases (TIMP)-3 using TIMP-1 as the scaffold: A new frontier in TIMP engineering Protein Sci., October 1, 2002; 11(10): 2493 - 2503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Hunt, G. M. Aru, M. R. Hayden, C. K. Moore, B. D. Hoit, and S. C. Tyagi Induction of oxidative stress and disintegrin metalloproteinase in human heart end-stage failure Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L239 - L245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Westling, A. J. Fosang, K. Last, V. P. Thompson, K. N. Tomkinson, T. Hebert, T. McDonagh, L. A. Collins-Racie, E. R. LaVallie, E. A. Morris, et al. ADAMTS4 Cleaves at the Aggrecanase Site (Glu373-Ala374) and Secondarily at the Matrix Metalloproteinase Site (Asn341-Phe342) in the Aggrecan Interglobular Domain J. Biol. Chem., May 3, 2002; 277(18): 16059 - 16066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. C. Neves-Ferreira, J. Perales, J. W. Fox, J. D. Shannon, D. L. Makino, R. C. Garratt, and G. B. Domont Structural and Functional Analyses of DM43, a Snake Venom Metalloproteinase Inhibitor from Didelphis marsupialis Serum J. Biol. Chem., April 5, 2002; 277(15): 13129 - 13137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Baker, D. R. Edwards, and G. Murphy Metalloproteinase inhibitors: biological actions and therapeutic opportunities J. Cell Sci., January 10, 2002; 115(19): 3719 - 3727. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
