Molecular studies of the biological and catalytic activities of ribonucleases.

摘要

Bovine pancreatic ribonuclease A (RNase A) catalyzes cleavage of RNA. Homologs of RNase A effect diverse biological phenomena. Onconase TM (ONC), an amphibian ribonuclease, is a potent toxin to cancer cells. Angiogenin (ANG), a ribonuclease present in human plasma, promotes angiogenesis. The cytotoxic activity of ONC and the angiogenic activity of ANG depend on their ribonucleolytic activity. This Dissertation describes factors that alter the ribonucleolytic activity, and consequently, the biological activities of ONC and ANG. Chapters Two and Three show that Ribonuclease Inhibitor (RI), a ubiquitous cytosolic protein, distinguishes ONC and other cytotoxic ribonucleases from their nontoxic homologs. Chapter Four shows that high conformational stability helps to preserve the catalytic activity of ONC within the cytosol and thereby contributes to its cytotoxicity. Chapter Five describes solution conditions, including pH and [Na+], that affect the catalytic activity of ANG. Definition of the factors that influence ribonucleolytic activity offers insight into the molecular mechanisms ribonuclease biology.