Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding partner of epithelial growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1). Implications for macular degenerations.

Détails

ID Serval
serval:BIB_9F0A371C5A98
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding partner of epithelial growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1). Implications for macular degenerations.
Périodique
Journal of Biological Chemistry
Auteur(s)
Klenotic P.A., Munier F.L., Marmorstein L.Y., Anand-Apte B.
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
07/2004
Peer-reviewed
Oui
Volume
279
Numéro
29
Pages
30469-30473
Langue
anglais
Notes
Publication types: Journal Article
Résumé
Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a matrix-bound inhibitor of matrix metalloproteinases. Mutations in the Timp-3 gene cause Sorsby fundus dystrophy (SFD), a hereditary macular degenerative disease. The pathogenic mechanisms responsible for the disease phenotype are unknown. In an in vivo quest for binding partners of the TIMP-3 protein in the subretina, we identified epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1, also known as fibulin 3) as a strong interacting protein. The COOH-terminal end of TIMP-3 was involved in the interaction. Interestingly, a missense mutation in EFEMP1 is responsible for another hereditary macular degenerative disease, Malattia Leventinese (ML). Both SFD and ML have strong similarities to age-related macular degeneration (AMD), a major cause of blindness in the elderly population of the Western hemisphere. Our results were supported by significant accumulation and expression overlap of both TIMP-3 and EFEMP1 between the retinal pigment epithelia and Bruch membrane in the eyes of ML and AMD patients. These results provide the first link between two different macular degenerative disease genes and imply the possibility of a common pathogenic mechanism behind different forms of macular degeneration.
Mots-clé
Animals, Cell Line, DNA, Complementary/metabolism, Extracellular Matrix Proteins/chemistry, Extracellular Matrix Proteins/metabolism, Genetic Vectors, Glutathione Transferase/metabolism, Humans, Immunoblotting, Immunohistochemistry, Macular Degeneration/genetics, Models, Genetic, Mutation, Missense, Pigment Epithelium of Eye/metabolism, Precipitin Tests, Protein Binding, Retina/metabolism, Swine, Tissue Inhibitor of Metalloproteinase-3/metabolism, Tissue Inhibitor of Metalloproteinase-3/physiology, Transfection, Two-Hybrid System Techniques
Pubmed
Web of science
Création de la notice
28/01/2008 13:54
Dernière modification de la notice
03/03/2018 20:02
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