Cathepsin S (EC 3.4.22.27)

Abstract In 1975 the name cathepsin S was given to a cysteine peptidase purified from bovine lymph nodes by Turnsek and co-workers [402] and in 1981 from spleen by Locnikar et a!. [355]. The enzyme showed similarities to cathepsin L, but differed in a number of respects, including pl, Mn pH stability, activity against synthetic substrates and sensitivity to inhibitors, as shown by Kirschke and Bromme and co-workers, 1984-1989 [93, 170, 172, 346]. In 1991 studies on the amino acid sequences by Ritonja et al. and \'viederanders and co-workers [1190, 1213] confirmed that cathepsins S and L are different enzymes. The name cathepsin S (EC 3.4.22.27) was recommended by the nomenclature committee of International Cnion of Biochemistry and Molecular Biology (IUBMB) in 1992. Cathepsin S is one of the lysosomal cysteine proteinases known so far to show a restricted tissue distribution. The highest levels have been detected in spleen, sessile lung macrophages and heart [34, 172,295,346, 1141, 1195], but the occurrence of the enzyme has also been described in ileum, brain, thyroid and ovary [1180]. Cathepsin S has been shown to be preferentially expressed in cells of mononuclear-phagocytic origin [1710] and overexpressed in cortical neurones and glia in samples of brain from patients with Alzheimer's disease [1684]. Cells doubly transfected with both p-amyloid precursor protein and cathepsin S, but not with the other cathepsins, secreted high levels of amyloid p-peptides, indicating a function of cathepsin S in the pathogenesis of Alzheimer's disease [1337]. Cathepsin S was also shown to be essential in B cells for effective proteolysis of the invariant chain necessary to render class II molecules competent for binding peptides [1345].