Intracellular routing of cytotoxic pancreatic-type ribonucleases.
In addition to their ribonucleolytic activity, several ribonucleases (RNases) play important roles in other specific biological activities, such as dendritic cell activation, certain pollen-induced allergies, blood vessel formation and defense against parasitic or microbial infections. Among these diverse actions, cytotoxic activity, which relies in most cases on ribonucleolytic activity, has attracted a considerable attention because of the potential for using RNases as therapeutic agents for the treatment of different malignancies. In addition to use naturally existing RNases, major efforts have been made in the development of engineered variants, which display more potent cytotoxic activity and greater selectivity for malignant cells. This review focuses on the molecular and cellular aspects of the internalization, intracellular trafficking and final sorting of cytotoxic RNases. Knowledge about the strategies used by these promising toxins provides us with essential information about the mechanisms that can be used to gain access to different subcellular compartments and intracellular sorting.
Benito
Antoni
A
Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Campus de Montilivi s/n 17071 Girona, Spain.
Vilanova
Maria
M
Ribó
Marc
M
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011485:Protein Binding; D015202:Protein Engineering; D021381:Protein Transport; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity
D000970:Antineoplastic Agents; D012259:Ribonuclease, Pancreatic