Human cystatin, a new protein inhibitor of cysteine proteinases

Brzin, Jože; Popović, Tatjana; Türk, Vito; Borchart, Ursula; Machleidt, Werner

doi:10.1016/0006-291x(84)91073-8

Cited by 171 publications

(71 citation statements)

References 17 publications

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“…Whereas the Leu-form exhibits the same inhibitory activity as the full-length Ser-forms, removal of Leu-7 and Leu-8 leads to an approximately 5000-fold lower affinity for papain. This is in agreement with our observation that a truncated form of human cystatin C [19] starting with Leu-Val-before the conserved Gly-ll (corresponding to Gly-9 of chicken cystatin) has virtually the same affinity for papain as the full-length form (Ki = 5 pM), whereas the truncated form starting with Gly-12 has been reported to be a more than 1000-fold weaker inhibitor [7]. One or two residues preceding the conserved Gly seem to be mainly responsible for the tighter binding of cystatins to papain.…”

Section: Discussionsupporting

confidence: 94%

Mechanism of inhibition of papain by chicken egg white cystatin

et al. 1989

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N-terminally truncated forms of chicken egg white cystatin and its cyanogen bromide fragments were isolated and assayed for inhibition of papain. Truncated forms beginning with Gly-9 and Ala-10 had a 5000-fold lower affinity for papain than the two isoelectric forms (pi=6.5 and 5.6) of the full-length inhibitor (K~--6 pM and 7 pM) or a truncated form beginning with Leu-7 (/~ = 6 pM), indicating the outstanding importance of one or two residues preceding conserved Gly-9 for binding. A weak inhibition of papain (K~ = 900 nM) was exhibited by the intermediate cyanogen bromide fragment (residues 30-89) containing the chicken cystatin QLVSG variation of the QWAG segment which is conserved in almost all members of the cystatin superfamily. The obtained affinity data provide independent evidence for the validity of the proposed docking model of a chicken cystatin-papain complex [( ) EMBO J. 7, 2593[( -2599.

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Section: Discussionsupporting

confidence: 94%

Mechanism of inhibition of papain by chicken egg white cystatin

et al. 1989

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“…The same authors found far higher serum concentrations in three dialysed patients than in healthy people that, combined with the rise in urinary concentrations observed in tubulopathy, suggested to them that although the physiology of the protein was completely unknown, it underwent glomerular filtration and was catabolised in the renal tubule. It was only after its amino acid sequence and molecular weight (13260 Da) were described in 1982 (8) that Brzin and colleagues noted the similarity between the protein and a cysteine proteinase inhibitor protein belonging to the cystatin family (9). This was subsequently confirmed by Barret and co-workers who renamed g trace protein ''cystatin C'' (10).…”

Section: Historymentioning

confidence: 98%

Cystatin C: current position and future prospects

Séronie-Vivien

Delanaye

Piéroni³

et al. 2008

Clinical Chemistry and Laboratory Medicine

164

145

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Cystatin C is a low-molecular-weight protein which has been proposed as a marker of renal function that could replace creatinine. Indeed, the concentration of cystatin C is mainly determined by glomerular filtration and is particularly of interest in clinical settings where the relationship between creatinine production and muscle mass impairs the clinical performance of creatinine. Since the last decade, numerous studies have evaluated its potential use in measuring renal function in various populations. More recently, other potential developments for its clinical use have emerged. This review summarises current knowledge about the physiology of cystatin C and about its use as a renal marker, either alone or in equations developed to estimate the glomerular filtration rate. This paper also reviews recent data about the other applications of cystatin C, particularly in cardiology, oncology and clinical pharmacology. Clin Chem Lab Med 2008;46:1664-86.

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“…The salivary cystatins -CST1, CST2, and CST4 -are perhaps the most surprising of the identified novel mediators of bone metastasis. Cystatins are cysteine protease inhibitors, with cystatin-C (CST3) potently inhibiting pro-metastatic Cathepsin B [61] and thus being considered to be a potential metastasis suppressor. The salivary cystatins, however, have not been shown to strongly antagonize Cathepsin B [62], and instead have been hypothesized to function in salivary glands as inhibitors of harmful proteinases expressed by pathogens [63].…”

Section: Mario Andres Blanco Et Al 1349mentioning

confidence: 99%

Global secretome analysis identifies novel mediators of bone metastasis

et al. 2012

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Bone is the one of the most common sites of distant metastasis of solid tumors. Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma. To comprehensively profile secreted proteins associated with bone metastasis, we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types. By comparing the secretomes of parental cells and their bone metastatic derivatives, we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines. We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis. Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1, CST2, and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

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Human cystatin, a new protein inhibitor of cysteine proteinases

Cited by 171 publications

References 17 publications

Mechanism of inhibition of papain by chicken egg white cystatin

Mechanism of inhibition of papain by chicken egg white cystatin

Cystatin C: current position and future prospects

Global secretome analysis identifies novel mediators of bone metastasis

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