Posttranslational Processing and Modification of Cathepsins and Cystatins

Abstract

Cathepsins are an essential protease family in all living cells. The cathepsins play an essential roles such as protein catabolism and protein synthesis. To targeting to various organella and to regulate their activity, the post translational-processing and modification play an important role Cathepsins are translated in polysome as the pre-pro-mature forms. The pre-peptide is removed cotranslationally and then translocated to Golgi-apparatus and the pro-part is removed and the mature-part is glycosylated, and the mature-part is targeted into the lysosome mediated by mannose-6-phosphate signal and the mature-part is bound with their coenzymes. The degradation of the mature-part is started by the limited proteolysis of the ordered nicked bonds to make hydrophobic peptides. The peptides are incorporated into phagosome or proteasome after ubiquitinated and are degrade into amino-acids. Cystatins are endogenous inhibitors of cathepsins. Cystatinαwhich is only located in skin is phosphorylated at the near C-terminus by protein kinase-C, and the phosphorylate-cystatinαis incorporated into cornified envelope and conjugated with filaggrin-fiber by transglutaminase to form the linker-fiber of skin. The cystatinαis modified by glutathione or make their dimmer, and they are inactive. Those modifications are regulated by the redox-potential by the glutathione.