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PRMT3 is a type I arginine methyltransferase that resides in the cytoplasm. A large proportion of this cystosolic PRMT3 is found associated with ribosomes. It is tethered to the ribosomes through its interaction with rpS2, which is also its substrate. Here we show that mouse embryos with a targeted disruption of PRMT3 are small in size but survive after(More)
PRMT3 (protein arginine methyltransferase 3) is one of four type I arginine methyltransferases that catalyse the formation of asymmetric dimethylarginine. PRMT3 is unique in that its N-terminus harbours a C2H2 zinc-finger domain that is proposed to confer substrate specificity. In addition, PRMT3 is the only type I enzyme that is restricted to the(More)
BACKGROUND & AIMS Prograstrin induces proliferation in colon crypts by activating p65nuclear factor-κB (NF-κB) (p65) and β-catenin. We investigated whether Annexin A2 (AnxA2), a progastrin receptor, activates NF-κB and β-catenin in vivo. METHODS ANXA2-null (ANXA2(-/-)) and wild-type (ANXA2(+/+)) mice were studied, along with clones of(More)
We hypothesize that tumor angiogenesis can be limited by the reduction of enzymatic activity of the urokinase type plasminogen activator. The proposed mechanism is elimination of proteolytic activity by the advancing tip of capillaries which utilize proteolysis to produce space needed for vessel expansion. To test our hypothesis, we have investigated the(More)
Proteolytic enzymes are required to mediate tumor cell invasion and metastasis. The urokinase plasminogen activator (uPA) is commonly overexpressed by many human cancers. Therefore, uPA is a logical target to inhibit cancer invasion and metastasis. However, uPA inhibitors also reduce tumor growth. We used a mutated form of plasminogen activator inhibitor(More)
We recently reported that overexpression of progastrin (PG) in embryonic epithelial cells (HEKmGAS cells) increased proliferation of the cells compared to that of control HEKC cells. Here, we report the novel finding that tumorigenic and metastatic potential of HEKmGAS cells is also increased significantly compared to that of HEKC cells. Cell(More)
To understand the fundamental determinants of urokinase plasminogen activator (uPA) driven angiogenesis in cancer we studied how inhibition of uPA activity could reduce neovascularization and consequently reduce tumor size in experimental animals. Proteolytic enzymes are required to mediate tumor cell invasion to adjacent tissues and initiate the metastatic(More)
Tissue-specific iron content is tightly regulated to simultaneously satisfy specialized metabolic needs and avoid cytotoxicity. In the brain, disruption of iron homeostasis may occur in acute as well as progressive injuries associated with neuronal dysfunction and death. We hypothesized that adverse effects of disrupted metal homeostasis on brain function(More)
Proteolytic activity driven by urokinase (uPA) is commonly recognized as an important factor in metastasis and angiogenesis. The eradication of unwanted uPA activity expressed by cancer cells results in the inhibition of metastasis and angiogenesis. Development of novel and highly selective uPA inhibitors could, therefore, produce new treatments of cancer.(More)