CTSL

CTSL Background

Cathepsin L (CTSL) is a lysosomal cysteine endopeptidase and is ubiquitously expressed in human tissues and cells ^[1]. CTSL is synthesized as pre-pro-cathepsin L, transported via the Golgi apparatus as pro-cathepsin L within secretory vesicles, and then stored as mature cathepsin L in lysosomes ^[2]. CTSL activation occurs by the removal of propeptides either by autocatalysis ^[3] or by aspartyl cathepsin D in the acidic lysosomal compartment ^[4]. Activated extracellular CTSL can hydrolyze extracellular matrix (ECM) proteins such as fibronectin, laminin, type I, IV, and XVIII collagen ^[5][6]. CTSL prefers to cleaving peptide bonds with aromatic residues in P2 and hydrophobic residues in the P3 position. And it possesses optimal catalytical activity at pH 3.0–6.5 in the presence of thiol compounds. Like other cysteine cathepsins, CTSL also takes part in lysosomal rupture-induced apoptosis. Deletion of CTSL retarded cell proliferation and tumor growth and remarkably reduced the tumor invasion ^[7]. CTSL may increase the ability of ovarian cancer cells to invade and metastasize in vitro ^[8]. Overexpression of CTSL is associated with invasiveness and/or tumorigenicity of various tumor cells, including breast, myeloma, melanoma, and glial tumor cells. Besides, CTSL plays a role in the immune system by degrading the Ii chain in MHC class II processing, which is a critical step in antigen presentation. The expression of CTSL in the thymus is essential for the development of natural killer cells ^[9]. And CTSL plays a part in recycling processes during axon outgrowth and synapse formation in the developing postnatal central nervous system.

[1] Bando Y, Kominami E, et al. Purification and tissue distribution of rat cathepsin L [J]. J Biochem. 1986;100(1):35–42.
[2] Collette J, Bocock JP, et al. Biosynthesis and alternate targeting of the lysosomal cysteine protease cathepsin L [J]. Int Rev Cytol. 2004; 241():1-51.  
[3] Jerala, R., Zerovnik, E., et al. pH-induced conformational transitions of the propeptide of humancathepsin L. A role for a molten globule state in zymogen activation [J]. J. Biol. Chem. 1998, 273, 11498–11504.
[4] Nishimura, Y., Kawabata, T., et al. Evidence that aspartic proteinase is involved in the proteolytic processing event of procathepsin L in lysosomes [J]. Arch. Biochem. Biophys. 1989, 271, 400–406.
[5] Mort JS. Handbook of proteolytic enzymes. In: Barrett AJ, Rawlings ND, Woessner JF, editors. San Diego: Academic; 1998. p. 609–17.
[6] Kirschke H. Handbook of proteolytic enzymes. Barrett AJ, Rawlings ND, Woessner JF, editors. San Diego: Academic; 1998. p. 617–21.
[7] Gocheva V, Zeng W, et al. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis [J]. Genes Dev. 2006 Mar 1; 20(5):543-56.
[8] Wang SM, Li L, et al. Relationship between cathepsin L and invasion and metastasis of ovarian carcinoma cells [J]. Zhonghua Fu Chan Ke Za Zhi. 2010 Aug; 45(8):598-602.
[9] Hsing LC, Rudensky AY The lysosomal cysteine proteases in MHC class II antigen presentation [J]. Immunol Rev. 2005 Oct; 207():229-41.