Caspase-1, also known as IL-1 beta-converting enzyme (ICE), is an aspartic protease that plays a key role in the inflammatory response and apoptosis. Caspase-1 precursor (about 50kDa) can be cleaved and the active enzyme consists of a complex of two 20 kDa (aa 120-297) and two 10 kDa (aa 317-404) subunits which associate following cleavage of inactive precursors. Caspase-1 is required for proteolytic cleavage of the IL-1 beta precursor to form the active proinflammatory cytokine. Alternate splicing generates several additional Caspase-1 isoforms with deletions in the propeptide regions or also in the mature subunits.
This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined.
Lysosomal carboxypeptidase, cathepsin A (protective protein, CathA), is a component of the lysosomal multienzyme complex along with beta-galactosidase (GAL) and sialidase Neu1, where it activates Neu1 and protects GAL and Neu1 against the rapid proteolytic degradation. Cathepsin A is a multicatalytic enzyme with deamidase and esterase in addition to carboxypeptidase activities. It was recently identified in human platelets as deamidase. In vitro, it hydrolyzes a variety of bioactive peptide hormones including tachykinins, suggesting that extralysosomal cathepsin A plays a role in regulation of bioactive peptide functions. It is a member of the alpha/beta hydrolase fold family and has been suggested to share a common ancestral relationship with other alpha/beta hydrolase fold enzymes, such as cholinesterases. Cathepsin A defects are linked to multiple forms of Galactosialidosis with a combined secondary deficiency of beta-galactosidase and neuraminidase. Cathepsin A is a key molecule in the onset of galactosialidosis and also highlight the therapeutic acts in vivo as an endothelin-1-inactivating enzyme and strongly confirm a crucial role of this enzyme in effective elastic fiber formation.
Cathepsin B (CatB) is an enzymatic protein belonging to the peptidase (or protease) families. It is the first described member of the family of lysosomal cysteine proteases. It is known to process a number of proteins, including pro and active caspases, prorenin and secretory leucoprotease inhibitor (SLPI). It is believed to participate in intracellular degradation and turnover of proteins. Cathepsin B may play a role in activation and inactivation of caspases, activation of renin and inactivation of SLPI, the key steps in apoptosis, angiotensin production, and progression of emphysema, respectively. Cathepsin B may also have a role in invasion and metastasis.
Cathepsin B is a papain-family cysteine protease that is normally located in lysosomes, where it is involved in the turnover of proteins and plays various roles in maintaining the normal metabolism of cells. This protease has been implicated in pathological conditions, e.g., tumor progression and arthritis. In disease conditions, increases in the expression of cathepsin B occur at both the gene and protein levels. Cathepsin B is synthesized as a preproenzyme and the primary pathways for its normal trafficking to the lysosome utilize mannose 6-phosphate receptors (MPRs). Mature cathepsin B has the ability to degrade several extracellular matrix components at both neutral and acidic pH and has been implicated in the progression of several human and rodent tumors progression and arthritis. Increased expression of cathepsin B in primary cancers, and especially in preneoplastic lesions, suggests that this enzyme might have pro-apoptotic features. Active cathepsin B is also secreted from tumours, a mechanism likely to be facilitated by lysosomal exocytosis or extracellular processing by surface activators. Cathepsin B is localized to caveolae on the tumour surface, where binding to the annexin II heterotetramer occurs. Thus CTSB is suggested as a tumor marker. Additionally, Cathepsin B can degrade extracellular matrix proteins, such as collagen IV and laminin, and can activate the precursor form of urokinase plasminogen activator (uPA), perhaps thereby initiating an extracellular proteolytic cascade.
Cathepsin B is a papain-family cysteine protease that is normally located in lysosomes , where it is involved in the turnover of proteins and plays various roles in maintaining the normal metabolism of cells. This protease has been implicated in pathological conditions , e.g. , tumor progression and arthritis. In disease conditions , increases in the expression of cathepsin B occur at both the gene and protein levels. Cathepsin B is synthesized as a preproenzyme and the primary pathways for its normal trafficking to the lysosome utilize mannose 6-phosphate receptors (MPRs). Mature cathepsin B has the ability to degrade several extracellular matrix components at both neutral and acidic pH and has been implicated in the progression of several Human and rodent tumors progression and arthritis. Cathepsin B expression is increased in many Human cancers at the mRNA , protein and activity levels. It is also frequently overexpressed in premalignant lesions , an observation that associates this protease with local invasive stages of cancer. Increased expression of cathepsin B in primary cancers , and especially in preneoplastic lesions , suggests that this enzyme might have pro-apoptotic features. Active cathepsin B is also secreted from tumours , a mechanism likely to be facilitated by lysosomal exocytosis or extracellular processing by surface activators. Cathepsin B is localized to caveolae on the tumour surface , where binding to the annexin II heterotetramer occurs. Thus CTSB is suggested as a tumor marker. Additionally , Cathepsin B can degrade extracellular matrix proteins , such as collagen IV and laminin , and can activate the precursor form of urokinase plasminogen activator (uPA) , perhaps thereby initiating an extracellular proteolytic cascade.
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