The RING finger domain of MDM2 is essential for MDM2-mediated TGF-beta resistance.

In this study, we attempt to gain insights into the molecular mechanism underlying MDM2-mediated TGF-beta resistance. MDM2 renders cells refractory to TGF-beta by overcoming a TGF-beta-induced G1 cell cycle arrest. Because the TGF-beta resistant phenotype is reversible upon removal of MDM2, MDM2 likely confers TGF-beta resistance by directly targeting the cellular machinery involved in the growth inhibition by TGF-beta.

Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation.

Upon vascular injury, locally controlled haemostasis prevents life-threatening blood loss and ensures wound healing. Intracellular material derived from damaged cells at these sites will become exposed to blood components and could contribute to blood coagulation and pathological thrombus formation. So far, the functional and mechanistic consequences of this concept are not understood.

Extracellular RNA is a natural cofactor for the (auto-)activation of Factor VII-activating protease (FSAP).

FSAP (Factor VII-activating protease) is a new plasma-derived serine protease with putative dual functions in haemostasis, including activation of coagulation Factor VII and generation of urinary-type plasminogen activator (urokinase). The (auto-)activation of FSAP is facilitated by polyanionic glycosaminoglycans, such as heparin or dextran sulphate, whereas calcium ions stabilize the active form of FSAP. In the present study, extracellular RNA was identified and characterized as a novel FSAP cofactor.

Factor VII-activating protease (FSAP) inhibits growth factor-mediated cell proliferation and migration of vascular smooth muscle cells.

The factor VII activating protease (FSAP) is a serine-protease present in human plasma that serves to activate single-chain plasminogen activators, as well as coagulation factor VII. FSAP was localized within atherosclerotic lesions, and a genetic polymorphism in FSAP is associated with carotid stenosis. Hence, this study was conducted to gain broader insights into the cellular effects of FSAP on vascular smooth muscle cells (VSMC).

Factor VII and single-chain plasminogen activator-activating protease: activation and autoactivation of the proenzyme.

Structural and biological characteristics of a recently described plasma serine protease, which displayed factor VII as well as pro-urokinase-activating properties in vitro, indicated a dual role for this factor VII-activating protease (FSAP) in hemostasis. Only the active protease (two-chain FSAP) has been isolated from plasma and from a prothrombin complex concentrate, whereas activators of the proenzyme have not been identified so far. After purification of the FSAP proenzyme from cryo-poor plasma by adsorption to an immobilized mAb and subsequent ion-exchange chromatography, activation to generate two-chain FSAP was followed by a direct chromogenic assay as well as by the ability of two-chain FSAP to activate pro-urokinase.