Transglutaminase-2: a new endostatin partner in the extracellular matrix of endothelial cells

Clément Faye , Antonio Inforzato , Marine Bignon , Daniel Hartmann , Laurent Muller , Lionel Ballut , Bjorn R Olsen , Anthony J Day , Sylvie Ricard-Blum (1)

1 IBCP - Institut de biologie et chimie des protéines [Lyon]

Endostatin, the C-terminal domain of collagen XVIII, binds to transglutaminase-2 (TG-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 to 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, R27 and R139, are crucial for its binding to TG-2. They are also involved in the binding to heparin (Sasaki et al., EMBO J 18:6240-6248), and to α5β1 and αvβ3 integrins (Faye et al., 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 GTP binding site of TG-2 as a potential binding site for endostatin. Endostatin and TG-2 are co-localized in the extracellular matrix secreted by endothelial cells under hypoxia, that stimulates angiogenesis. This interaction occurring in a cellular context might participate in the concerted regulation of angiogenesis, and tumorigenesis by the two proteins.

Mots clés: Life Sciences

Clément Faye, Antonio Inforzato, Marine Bignon, Daniel Hartmann, Laurent Muller, et al.. Transglutaminase-2: a new endostatin partner in the extracellular matrix of endothelial cells. Biochemical Journal, 2010, 427 (3), pp.467-475. ⟨10.1042/BJ20091594⟩. ⟨hal-00479272⟩