Disease relevance of RNASET2

• Tumor and metastasis suppression by the human RNASET2 gene [1].
• Moreover, we have extended our previous studies by evaluating the effect of RNASET2 on the metastatic behavior of the highly-invasive ovarian cancer cell line HEY3MET2 [1].
• RNASET2 is endowed with catalytic activity as demonstrated with purified recombinant protein expressed in the Baculovirus Expression Vector System and in a human cell line ectopically expressing various types of constructs [2].

High impact information on RNASET2

• Enzyme catalyzed hydrolysis of the nonamers with ribonuclease T2 showed that the linkage at the ribonucleotide was the desired 3'-5'. A control nonamer with a 2'-5' linkage was subjected to the enzyme, and showed no cleavage [3].
• Digestion with ribonuclease T2 has been used to study the size of poly(U) protected by ribosome binding [4].
• We show that RNASET2 is present in multiple forms in human cell lines and mouse tissues, one of which represents the full length, glycosylated and secreted form, while the others are proteolytic products [2].
• In this study, we have started the cellular and biochemical characterization of RNASET2 and showed that it is a secreted glycoprotein [1].
• Moreover, RNASET2-mediated suppression of tumorigenesis and metastasis was not affected by a double point mutation targeted to the putative ribonuclease catalytic sites, suggesting that tumor suppression by RNASET2 is not mediated by its ribonuclease activity [1].

Biological context of RNASET2

• BACKGROUND.: Human RNASET2 is a T(2)-RNase glycoprotein encoded by the RNASET2 gene, which is located on chromosome 6 (6q27) [5].
• Steady-state kinetic studies of binding and catalysis by ribonuclease T2: a microenvironmental survey of the active site by using a series of adenosine-3'- and -5'-alkylphosphates [6].

Anatomical context of RNASET2

• From such analysis, RNASET2 was found to significantly decrease the metastatic potential of this cell line in vivo [1].
• RNASET2 significantly inhibited clonogenicity in HT29 cells [5].
• Three proteins expressed in normal mucosa, but lost in primary cancer and hepatic metastasis, were recognized as calmodulin, ribonuclease 6 precursor and mannosidase-alpha [7].

Associations of RNASET2 with chemical compounds

• BACKGROUND.: A synthetic RNASET2 gene that was optimized for expression in the yeast Pichia pastoris was designed according to the cDNA sequence and was cloned under the control of the methanol-induced promoter fused to the alpha-mating secretion peptide [5].
• Production of the substrate to a high degree of purity has been achieved using apo-glucose oxidase to specifically remove contaminating flavin adenine dinucleotide from solution and hydrolysis of a cyclic intermediate as a final production protocol by ribonuclease T2 to give the product in high yield [8].

Other interactions of RNASET2

• In HUVE cells, RNASET2 inhibited angiogenin-, bFGF-, and VEGF-induced tube formation in a dose-dependent manner [5].
• Because the homozygous deletion might affect the expression of nearby genes, we analyzed the expression of the two closest known genes flanking the deletion, RNASE6PL and RSK-3 [9].

Analytical, diagnostic and therapeutic context of RNASET2

• Partial purification and immobilization of ribonuclease T2 [10].
• The use of continuous ultrafiltration reactors at each stage is described and compared to a final production step utilizing immobilized ribonuclease T2 [8].

References