Genetic polymorphisms of the CST2 locus coding for cystatin SA

Shintani, Masuro; Minaguchi, Kiyoshi; Isemura, Satoko; Saitoh, Eiichi; Sanada, Kazuo; Semba, Toshihiko

doi:10.1007/bf02272840

Cited by 14 publications

(16 citation statements)

References 29 publications

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“…A limited number of polymorphisms affecting the coding sequence of human SD-type cystatins have been found. Two alleles at the CST2 locus (encoding cystatin SA) are known (Shintani et al, 1994;Saitoh et al, 1998;Haga and Minaguchi, 1999). CST2*1 and CST*2 differ by two point mutations: a GàA transition in exon 2, and an AàT transversion in exon 3.…”

Section: (A) Polymorphismsmentioning

confidence: 99%

Salivary (SD-Type)Cystatins:OverOneBillionYears in theMaking—But toWhatPurpose?

Dickinson

2002

Critical Reviews in Oral Biology & Medicine

101

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The cystatin superfamily is comprised of a large group of ancestrally related proteins, most of which are potent inhibitors of cysteine peptidases (CPs). Human saliva contains relatively abundant proteins that are related ancestrally in sequence to the cystatin superfamily. These proteins are now commonly referred to as 'salivary cystatins', although this is something of a misnomer (see below). It has been several years since the publication of the last comprehensive reviews that focused on the salivary cystatins (Bobek and Levine, 1992;Henskens et al., 1996c). Since then, significant advances have been made regarding the gene organization, protein structure, and properties of human and rat proteins. Therefore, a major purpose of this article is to review this recent work. What is the function of the 'salivary cystatins'? Despite a great deal of research effort, we still do not have a definitive answer to this question. A major impediment is the lack of a disease to associate with a specific defect in a gene: Functionality must be inferred from circumstantial evidence. A central premise of this review is that clues to 'salivary cystatin' function are contained within their phylogenetic history, and that by looking at established or likely functions of their 'siblings' and 'cousins', one can assess the likelihood of this function(s) continuing into the 'salivary cystatins'. A comprehensive review of the large cystatin superfamily is beyond the scope of a single article. This review will aim to outline the main branches of the superfamily and the common elements of their structure and function, but will pay closest attention to the nearest relatives of the 'salivary cystatins'.(1) BACKGROUND Scission of peptide bonds is an essential reaction in living cells, and there is a considerable number of peptidases that catalyze this reaction with various degrees of specificity. CPs use a cysteine residue in the active site as the nucleophile in the reaction (see Dickinson, 2002, and references therein). Release of proteolytic enzymes outside of their normal compartment has the potential to cause serious degradation and pathology-an effect taken advantage of by pathogenic organisms from a wide range of phyla. Therefore, control of proteolytic enzyme activity is mandatory. Building upon a very early report (see Barrett et al., 1986, for a review of this earlier literature) of a bovine trypsin inhibitor in chicken egg white, a search for egg white inhibitors of plant proteinases (the CPs ficin and papain) identified a relatively small (12.7 kDa) protein that was a potent inhibitor (Ki = 10 nM). The term cystatin was coined for this protein, which was shown also to inhibit mammalian CPs of the papain superfamily, including cathepsins B, C, H, and L. Cystatins form 1:1 reversible complexes with CPs, in competition with the substrate, but in some cases the binding is so tight as to be physiologically irreversible. (2) THE CYSTATIN SUPERFAMILYExamination of mammalian tissues and serum revealed several CP inhibitors ranging in si...

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Section: (A) Polymorphismsmentioning

confidence: 99%

Salivary (SD-Type)Cystatins:OverOneBillionYears in theMaking—But toWhatPurpose?

Dickinson

2002

Critical Reviews in Oral Biology & Medicine

101

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“…Cystatin SA1 (common cystatin SA; Isemura et al, 1986), cystatin SA2 (a variant of cystatin SA, which carries two amino acid substitutions: 59 Gly → Asp, 120 Glu → Asp; Shintani et al, 1994;Haga and Minaguchi, 1999), and cystatin S were recombinant proteins purified from periplasmic fractions of transformed Escherichia coli cells as described previously Saitoh et al, 1998). Cystatin A purified from human placenta, cystatin B and cystatin C from human plasma were purchased from BioPur AG, Bubendorf, Switzerland.…”

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confidence: 99%

Cytokine-Inducing Activity of Family 2 Cystatins

Kato¹,

Imatani²,

Miura³

et al. 2000

Biological Chemistry

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Cystatins are physiological cysteine proteinase inhibitors. Here we report a novel function for some family 2 cystatins that is not related to these activities. The release of interleukin-6 (IL-6) and interleukin-8 (IL-8) by the gingival fibroblasts and that of IL-6 by murine splenocytes were measured using ELISA systems specific for these cytokine molecules. Family 2 cystatins, including cystatins C, SA1, SA2, S, and egg white cystatin, upregulated the IL-6 production by two-lasts at physiological concentrations. After complete saturation with papain, those family 2 cystatins still upregulated IL-6 production, suggesting that the papain-inhibitory site was not involved in the cytokine-inducing activity.

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“…The presence of genetic polymorphisms in the human type 2 cystatin gene family has been demonstrated in the CST3, CST5, and CST2 genes [4][5][6][7][8]13,17,23) , and a number of single nucleotide polymorphisms (SNPs) related to the type 2 cystatin gene family have been submitted in the JSNP database (the database of Japanese single nucleotide polymorphism) with recent progress on genomic sequencing: 1 SNP for CST1, 4 for CST3, 4 for CST4, 5 for CST5. In this paper, we report a RFLP related to the CST2 gene, and also show a relationship with the previously reported cystatin SA protein polymorphism 23) . After informed consent was obtained, blood and saliva samples were collected from 86 subjects, and genomic DNA was obtained from the blood by usual Phenol/Chloroform extraction method.…”

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confidence: 99%

“…The filters were exposed two days on Kodak X-OMAT TM AR radiographic film. Salivary cystatin protein polymorphism was typed as previously described 23) . By Southern hybridization using exon 1 and exon 2 probes, no difference was observed with the exon 1 probe, but a distinct difference was observed in 8.3 kb and 3.5 kb bands using the exon 2 probe (Fig.…”

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confidence: 99%

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SAC I Restriction Fragment Length Polymorphism (RFLP) Related to the Human CST2 Gene.

Minaguchi

Kiriyama

Saitoh

et al. 2002

Bull. Tokyo Dent. Coll.

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Restriction Fragment Length Polymorphism (RFLP) related to cystatin gene (CST) family was detected in the Japanese population by using restriction enzyme Sac I. A polymorphic site, located at 0.9 kb from the 3Ј end of the CST2 gene, revealed a two allele polymorphism with band sizes of 3.5kb and 8.3kb by hybridization with probe including exon 2 of the CST1 gene. The gene frequencies in the Japanese population were 0.326 for 3.5 kb allele and 0.674 for 8.3kb allele (n‫.)68ס‬ The phenotypes of the polymorphism showed no association with the previously reported electrophoretic cystatin SA protein phenotypes 22) .

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Genetic polymorphisms of the CST2 locus coding for cystatin SA

Cited by 14 publications

References 29 publications

Salivary (SD-Type)Cystatins:OverOneBillionYears in theMaking—But toWhatPurpose?

Salivary (SD-Type)Cystatins:OverOneBillionYears in theMaking—But toWhatPurpose?

Cytokine-Inducing Activity of Family 2 Cystatins

SAC I Restriction Fragment Length Polymorphism (RFLP) Related to the Human CST2 Gene.

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