CTSS

CTSS Background

Cathepsin S (CTSS) is one of the lysosomal cysteine endopeptidases. CTSS is synthesized as a 331 amino acid pre-proenzyme containing a signal domain (16 amino acids), pro-peptide domain (98 amino acids), and mature domain (217 amino acids) ^[1]. The propeptide domain occludes the active site, rendering the protease inactive ^[2]. Procathepsin S can be autocatalytically activated ac pH 4.5 ^[3]. And active CTSS is overexpressed and secreted by human chondrocytes upon stimulation from pro-inflammatory cytokines interleukin 1α (IL-1α) and tumor necrosis factor α (TNF α) ^[13]. CTSS has a high endopeptidase activity against different proteins including elastin and collagen. Its substrate specificity is similar to cathepsin L, but it differs distinctly in its S2 subsite specificity ^[4]. Biochemically, cathepsin S is different from other cysteine cathepsins in its ability to retain activity at a neutral pH ^[5]. CTSS is predominantly expressed in the spleen and professional antigen-presenting cells, including B lymphocytes, macrophages, and other class II-positive cells ^[6][7]. The restricted tissue distribution of CTSS is consistent with its function in the major histocompatibility complex (MHC) class II antigen-presenting pathway in antigen-presenting cells derived from bone marrow ^[8]. CTSS is essential in B cells for effective Ii chain proteolysis necessary to make class II molecules competent to bind peptides ^[9]. And CTSS is also involved in lysosomal rupture-induced apoptosis. CTSS was shown to play novel roles in cancer cell migration and invasion, such as colorectal carcinomas ^[10], gastric cancer ^[11], and hepatocellular carcinoma ^[12]. Silencing CTSS expression inhibited the migration and invasion of gastric cancer cells in vitro. Flannery T et al. demonstrated that CTSS may act as a prognostic indicator and potential target for noninvasive therapy ^[14].

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[7] Shi GP, Webb AC, et al. Human cathepsin S: chromosomal localization, gene structure, and tissue distribution [J]. J Biol Chem. 1994 Apr 15; 269(15):11530-6.
[8] Honey, K., and Rudensky, A. Y. Lysosomal cysteine proteases regulate antigen presentation [J]. Nat. Rev. Immunol. 2003, 3, 472 - 482.
[9] ERiese RJ, Wolf PR, et al. sential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading [J]. Immunity. 1996 Apr; 4(4):357-66.
[10] Burden RE, Gormley JA, et al. Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas [J]. Biochimie. 2012 Feb; 94(2):487-93.
[11] Yang Y, Lim SK, et al. Cathepsin S mediates gastric cancer cell migration and invasion via a putative network of metastasis-associated proteins [J]. J Proteome Res. 2010 Sep 3; 9(9):4767-78.
[12] Fan Q, Wang X, et al. Silencing cathepsin S gene expression inhibits growth, invasion, and angiogenesis of human hepatocellular carcinoma in vitro [J]. Biochem Biophys Res Commun. 2012 Sep 7; 425(4):703-10.
[13] Cagliˇc, D.; Repnik, U.; et al. The proinflammatory cytokines interleukin-1α and tumor necrosis factorα promote the expression and secretion of proteolytically active cathepsin S from human chondrocytes [J]. Biol. Chem. 2013, 394, 307-316.
[14] Flannery T, McQuaid S, et al. Cathepsin S expression: An independent prognostic factor in glioblastoma tumours--A pilot study [J]. Int J Cancer. 2006 Aug 15; 119(4):854-60.