Showing papers by "Sylvie Ricard-Blum published in 2010"
TL;DR: Inhibition experiments support the hypothesis that the GTP-binding site of TG-2 is a potential binding site for endostatin, and this interaction might participate in the concerted regulation of angiogenesis and tumorigenesis by the two proteins.
Abstract: Endostatin, a C-terminal fragment of collagen XVIII, binds to TG-2 (transglutaminase-2) in a cation-dependent manner. Recombinant human endostatin binds to TG-2 with an affinity in the nanomolar range (Kd=6.8 nM). Enzymatic assays indicated that, in contrast with other extracellular matrix proteins, endostatin is not a glutaminyl substrate of TG-2 and is not cross-linked to itself by the enzyme. Two arginine residues of endostatin, Arg27 and Arg139, are crucial for its binding to TG-2. They are also involved in the binding to heparin [Sasaki, Larsson, Kreuger, Salmivirta, Claesson-Welsh, Lindahl, Hohenester and Timpl (1999) EMBO J. 18, 6240-6248], and to alpha5beta1 and alphavbeta3 integrins [Faye, Moreau, Chautard, Jetne, Fukai, Ruggiero, Humphries, Olsen and Ricard-Blum (2009) J. Biol. Chem. 284, 22029-22040], suggesting that endostatin is not able to interact simultaneously with TG-2 and heparan sulfate, or with TG-2 and integrins. Inhibition experiments support the hypothesis that the GTP-binding site of TG-2 is a potential binding site for endostatin. Endostatin and TG-2 are co-localized in the extracellular matrix secreted by endothelial cells under hypoxia, which stimulates angiogenesis. This interaction, occurring in a cellular context, might participate in the concerted regulation of angiogenesis and tumorigenesis by the two proteins.
54 citations
TL;DR: In this article, surface plasmon resonance (SPR) binding assays, cell attachment assays as well as immunofluorescence and activity assays were performed, all indicating that the NTR domain can mediate PCPE-1 binding to cell surface heparan sulfate proteoglycans (HSPGs).
35 citations
TL;DR: The integration of existing intracellular interaction networks with the extracellular interaction network the authors have developed (MatrixDB, http://matrixdb.ibcp.fr) will contribute to provide further insights into the global mechanisms of aging.
Abstract: Biological systems are made up of very large numbers of different components interacting at various scales. Most genes, proteins and other cell components carry out their functions within a complex network of interactions and a single component can affect a wide range of other components. Interactions involved in biological processes have been first characterized individually but this “reductionist” approach suffers from a lack of information about time, space, and context in which the interactions occur in vivo. A global, integrative, approach has been developed for several years, focusing on the building of protein–protein interaction maps or interactomes. These interaction networks are complex systems, where new properties arise. They are part of the emergent field of systems biology, which focuses on studying complex biological systems such as a cell or organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions. Aging is associated with many diseases, such as cancer, diabetes, cardiovascular and neurodegenerative disorders and this limits the investigation of the mechanisms underlying the aging process when focusing on a single gene or a single biochemical pathway. The integration of existing intracellular interaction networks with the extracellular interaction network we have developed (MatrixDB, http://matrixdb.ibcp.fr
) will contribute to provide further insights into the global mechanisms of aging.
20 citations