title: Human genetic diseases of proteolysis.
abstract: Although in the past protein stability commonly has been considered an inherent property of a given protein, the truth is far more complex. Elaborate enzymatic systems exist in multiple intracellular compartments to hydrolyze proteins. These systems are capable of providing a sensitive mechanism to regulate protein expression, a mechanism that is complementary to the transcriptional and translational control mechanisms that influence protein synthesis. The power of regulated proteolysis has been well-demonstrated in the abrupt degradation of cyclins that underlies eukaryotic cell cycle progression. Coincidental with the recent rapid gains in understanding proteolysis at a biochemical level, several human diseases have been found to result from disordered proteolysis. This article reviews several examples of human disease resulting from mutations of genes encoding serine proteases, cysteine proteases, and their inhibitors. Examples are also presented of human diseases resulting from disorders in the highly intricate ubiquitin-proteasome pathway of protein degradation. It is certain that many more human diseases will be associated in the future with disorders of proteolysis.
authors: Division of Pediatric Hematology, Johns Hopkins University School of Medicine, and the Johns Hopkins Oncology Center, Baltimore, Maryland, USA. gkato@jhmi.edu
authors: G J
authors: GJ
authors: Kato
mesh_terms: D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010450:Endopeptidases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D030342:Genetic Diseases, Inborn / Q000201:enzymology*; D020022:Genetic Predisposition to Disease / Q000201:enzymology; D006801:Humans; D006868:Hydrolysis; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D010450:Endopeptidases; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases