Cathepsin S from bovine spleen. Purification, distribution, intracellular localization and action on proteins

Kirschke, Heidrun; Wiederanders, Bernd; Brὂmme, Dieter; Rinne, Ari

doi:10.1042/bj2640467

Cited by 189 publications

(120 citation statements)

References 19 publications

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“…Membranes were stained with Ponceau red to confirm equal loading of supernatants. (27) and that cathepsin L activity can be stabilized by p41 extracellularly (28) suggest that secreted cathepsin L -like species might play a role in cell invasion. Indeed, a substantial amount of evidence points toward their role in the degradation of elastin, collagen, laminin, and other components of the extracellular matrix (29 -33).…”

Section: Discussionmentioning

confidence: 99%

Recombinant cathepsin S propeptide attenuates cell invasion by inhibition of cathepsin L–like proteases in tumor microenvironment

Burden¹,

Snoddy

Buick

et al. 2008

Molecular Cancer Therapeutics

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Human cathepsin L along with cathepsin S, K, and V are collectively known as cathepsin L -like proteases due to their high homology. The overexpression and aberrant activity of each of these proteases has been implicated in tumorigenesis. These proteases contain propeptide domains that can potently inhibit both their cognate protease and other proteases within the cathepsin L -like subfamily. In this investigation, we have produced the cathepsin S propeptide recombinantly and have shown that it is a potent inhibitor of the peptidolytic, elastinolytic, and gelatinolytic activities of the cathepsin L -like proteases. In addition, we show that this peptide is capable of significantly attenuating tumor cell invasion in a panel of human cancer cell lines. Furthermore, fusion of an IgG Fc-domain to the COOH terminus of the propeptide resulted in a chimeric protein with significantly enhanced ability to block tumor cell invasion. This Fc fusion protein exhibited enhanced stability in cell-based assays in comparison with the unmodified propeptide species. This approach for the combined inhibition of the cathepsin L -like proteases may prove useful for the further study in cancer and other conditions where their aberrant activity has been implicated. Furthermore, this strategy for simultaneous inhibition of multiple cysteine cathepsins may represent the basis for novel therapeutics to attenuate tumorigenesis. [Mol Cancer Ther 2008;7(3):538 -47]

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Section: Discussionmentioning

confidence: 99%

Recombinant cathepsin S propeptide attenuates cell invasion by inhibition of cathepsin L–like proteases in tumor microenvironment

Burden¹,

Snoddy

Buick

et al. 2008

Molecular Cancer Therapeutics

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“…No loss of activity occurred after 4 hours at 40°C at pH values up to 7.0, while these other cathepsins are inactivated. Only 10-12% of the activity was lost in 1 hour at pH 7.5 (Kirschke et al, 1989;Brömme et al, 1993). Cystatins and stefins are potent inhibitors of cathepsin S (Brömme et al, 1991;Turk et al, 1994).…”

Section: (A) Cathepsin S (I) Properties and Tissue Distributionmentioning

confidence: 99%

Cysteine Peptidases of Mammals: Their Biological Roles and Potential Effects in the Oral Cavity and Other Tissues in Health and Disease

Dickinson

2002

Critical Reviews in Oral Biology & Medicine

158

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Cysteine peptidases (CPs) are phylogenetically ubiquitous enzymes that can be classified into clans of evolutionarily independent proteins based on the structural organization of the active site. In mammals, two of the major clans represented in the genome are: the CA clan, whose members share a structure and evolutionary history with papain; and the CD clan, which includes the legumains and caspases. This review focuses on the properties of these enzymes, with an emphasis on their potential roles in the oral cavity. The human genome encodes at least (but possibly no more than) 11 distinct enzymes, called cathepsins, that are members of the papain family C1A. Ten of these are present in rodents, which also carry additional genes encoding other cathepsins and cathepsin-like proteins. Human cathepsins are best known from the ubiquitously expressed lysosomal cathepsins B, H, and L, and dipeptidyl peptidase I (DPP I), which until recently were considered to mediate primarily "housekeeping" functions in the cell. However, mutations in DPP I have now been shown to underlie Papillon-Lefèvre syndrome and pre-pubertal periodontitis. Other cathepsins are involved in tissue-specific functions such as bone remodeling, but relatively little is known about the functions of several recently discovered enzymes. Collectively, CPs participate in multiple host systems that are active in health and in disease. They are involved in tissue remodeling and turnover of the extracellular matrix, immune system function, and modulation and alteration of cell function. Intracellularly, CPs function in diverse processes including normal protein turnover, antigen and proprotein processing, and apoptosis. Extracellularly, they can contribute directly to the degradation of foreign proteins and the extracellular matrix. However, CPs can also participate in proteolytic cascades that amplify the degradative capacity, potentially leading to pathological damage, and facilitating the penetration of tissues by cancer cells. We know relatively little regarding the role of human CPs in the oral cavity in health or disease. Most studies to date have focused on the potential use of the lysosomal enzymes as markers for periodontal disease activity. Human saliva contains high levels of cystatins, which are potent CP inhibitors. Although these proteins are presumed to serve a protective function, their in vivo targets are unknown, and it remains to be discovered whether they serve to control any human CP activity.

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“…For direct primary structure analysis cathepsin S was purified from bovine spleen as described [3]. The purified enzyme (2yg) was subjected to 24 cycles in the sequencer.…”

Section: Resultsmentioning

confidence: 99%

“…Cathepsin S was purified from bovine spleen as described previously [3]. The purified protein (25pg) was alkylated with 4-vinylpyridine [S] and desalted by reversed phase chromatography on a 0.46 x 3 cm TSK TMS250 (Cl) column.…”

Section: Purification Alkylation and Tryandn Digestion Of Cathepsin Smentioning

confidence: 99%

“…The cathepsins B (EC 3.4.22.1), H (EC 3.4.22.16) and L (EC 3.42215) are the best characterized enzymes of this group [l]. The recently described cathepsin S [2,3] has a high specific activity towards protein substrates, a property it shares with cathepsin L. However, cathepsin S differs from cathepsin L since it is a single chain enzyme like papain. Furthermore, it differs from all cysteine proteinases since it is stable and active in vitro at neutral pH.…”

Section: Introductionmentioning

confidence: 99%

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Primary structure of bovine cathepsin S Comparison to cathepsins L, H, B and papain

Wiederanders¹,

Broemme²,

Kirschke³

et al. 1991

FEBS Letters

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The primary structure of bovine cathepsin S was determined by combining results of protein and peptide sequencing with the sequence deduced from nucleic acid sequencing. Using polymerase chain reaction (J-CR) technology, cDNA clones commencing at amino acid 22 of the mature enzyme and continuing through the 3' untranslated region of bovine cathepsin S mRNA were isolated and sequenced. The open reading frame in these overlapping clones correctly predicts the determined amino acid sequence of 13 tryptic peptides derived from purified bovine spleen cathepsin S. The deduced amino acid sequence shows that mature bovine cathepsin S consists of 217 amino acids corresponding to a molecular weight of 23.7 kDa. Cathepsin S belongs to the papain superfamily of lysosomal cysteine proteinases and shares 41% identity with papain. Amino acid sequence identities of bovine cathepsin S to human cathepsins L, H, and I3 are 56%, 47% and 31% respectively.

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Cathepsin S from bovine spleen. Purification, distribution, intracellular localization and action on proteins

Cited by 189 publications

References 19 publications

Recombinant cathepsin S propeptide attenuates cell invasion by inhibition of cathepsin L–like proteases in tumor microenvironment

Recombinant cathepsin S propeptide attenuates cell invasion by inhibition of cathepsin L–like proteases in tumor microenvironment

Cysteine Peptidases of Mammals: Their Biological Roles and Potential Effects in the Oral Cavity and Other Tissues in Health and Disease

Primary structure of bovine cathepsin S Comparison to cathepsins L, H, B and papain

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