|Human, Mouse, Rat|
Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting
Background: Argininosuccinate synthetase (ASS1) catalyzes the formation of argininosuccinate from citrulline and aspartate, the rate-limiting step in the urea cycle that is responsible for the synthesis of arginine and the clearance of nitrogenous waste (1). ASS1 is ubiquitously and differentially expressed in different cell types and tissues. Mutations in ASS1 are associated with citrullinemia type I, an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels in human patients (2, 3).Loss of ASS1 expression is one of the common metabolic alterations observed in many cancers, and it is a prognostic biomarker of reduced metastasis-free survival. ASS1 deficiency leads to the dependence of extracellular arginine for survival, proliferation, and cell growth. Ariginine starvation induces autophagy and apoptosis in ASS1 deficient cells and this has been exploited as a therapeutic intervention for the tumors with loss of ASS1 expression (4, 5). Pegylated arginine deiminase (ADI-PEG20), an enzyme that degrades arginine into citrulline, causes significant growth inhibition in tumors that have lost ASS1 expression, such as hepatocellular carcinoma, breast cancer, and sarcoma (6-8).
|Human, Mouse, Rat|
Application Methods: Immunoprecipitation, Western Blotting
Background: Mitochondrial carriers are integral proteins of the mitochondrial inner membrane that transport metabolites, nucleotides, and co-factors between the cytosol and the mitochondria (1). The calcium-binding mitochondrial carrier protein ARALAR (SLC25A12, AGC1) is an aspartate-glutamate exchange protein responsible for transporting mitochondrial aspartate across the mitochondrial inner membrane in exchange for cytosolic glutamate (2,3). ARALAR and other proteins of the aspartate-glutamate carrier (AGC) group are required for the transfer of mitochondrial aspartate to the cytosol, a key step in urea synthesis (4). Research studies using ARALAR-knockout mice indicate that ARALAR plays an important role in proper CNS myelination. Mice lacking ARALAR suffer from hypomyelination as a result of a lack of oligodendrocyte maturation caused by decreased brain N-acetylaspartate levels (5). Mutation of the corresponding SLC25A12 gene can result in global cerebral hypomyelination and severe psychomotor retardation, caused by deficient ARALAR activity and limited mitochondrial aspartate efflux (6).