Squamous cell carcinoma antigen is a potent inhibitor of cysteine proteinase cathepsin L

Takeda, Atsushi; Yamamoto, Takako; Nakamura, Yoshiko; Takahashi, T.; Hibino, Toshihiko

doi:10.1016/0014-5793(94)01456-b

Cited by 55 publications

(41 citation statements)

References 23 publications

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“…Based on the presence of consensus proximal hinge motifs each of these serpins is likely to be a proteinase inhibitor, but in the absence of functional data possible targets of these serpins cannot easily be predicted. It should be noted, however, that recent studies have shown that serpins are capable of inhibiting more than one class of proteinase (34,41). Hence the cognate proteinases of these mouse serpins may include serine proteinases and cysteine proteinases (caspases or papain-like cathepsins).…”

Section: Discussionmentioning

confidence: 99%

A New Family of 10 Murine Ovalbumin Serpins Includes Two Homologs of Proteinase Inhibitor 8 and Two Homologs of the Granzyme B Inhibitor (Proteinase Inhibitor 9)

Sun

Ooms

Bird

et al. 1997

Journal of Biological Chemistry

107

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Serine proteinase inhibitors (serpins) are classically regulators of extracellular proteolysis, however, recent evidence suggests that some function intracellularly. Such "ovalbumin" serpins include the human proteinase inhibitors 6 (PI-6), 8 (PI-8), and 9 (PI-9), plasminogen activator inhibitor 2, and the monocyte/neutrophil elastase inhibitor. PI-9 is a potent granzyme B (graB) inhibitor that has an unusual P 1 Glu and is present primarily in lymphocytes. In a search for the murine equivalent of PI-9 we screened cDNA libraries, and performed reverse transcriptase-polymerase chain reaction on RNA isolated from leukocyte cell lines and from lymph nodes and spleens of allo-immunized mice. We identified 10 new ovalbumin serpin sequences: two resemble PI-8, two resemble PI-9, and the remaining six have no obvious human counterparts. By RNA analysis only one of the two sequences resembling PI-9 (designated SPI6) is present in mouse lymphocytes while the other (a partial clone designated mBM2A) is predominantly in testis. SPI6 comprises a 1.8-kilobase cDNA encoding a 374-amino acid polypeptide that is 68% identical to PI-9. mBM2A is 65% identical to PI-9 and over 80% identical to SPI6. Although the reactive loops of SPI6 and mBM2A differ from PI-9, both contain a Glu in a region likely to contain the P 1 -P 1 bond. SPI6 produced in vitro using a coupled transcription/translation system formed an SDS-stable complex with human graB and did not interact with trypsin, chymotrypsin, leukocyte elastase, pancreatic elastase, thrombin, or cathepsin G. Recombinant SPI6 produced in a yeast expression system was used to examine the interaction with human graB in more detail. The second-order rate constant for the interaction was estimated as 8 ؋ 10 4 M ؊1 s ؊1 , and inhibition depended on the Glu in the SPI6 reactive center. The SPI6 gene was mapped to the same region on mouse chromosome 13 as Spi3, which encodes the murine homolog of PI-6. We conclude that even though their reactive centers are not highly conserved, SPI6 is a functional homolog of PI-9, and that the regulation of graB in the mouse may involve a second serpin encoded by mBM2A. Our identification of multiple sequence homologs of PI-8 and PI-9, and six new ovalbumin serpins, is consonant with the idea that the larger set of granule and other proteinases known to exist in the mouse (compared with human) is balanced by a larger array of serpins.

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Section: Discussionmentioning

confidence: 99%

A New Family of 10 Murine Ovalbumin Serpins Includes Two Homologs of Proteinase Inhibitor 8 and Two Homologs of the Granzyme B Inhibitor (Proteinase Inhibitor 9)

Sun

Ooms

Bird

et al. 1997

Journal of Biological Chemistry

107

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“…This would suggest that leupin may inhibit a chymotrypsin-like protease. However, SCCA has recently been found to inhibit the cysteine proteases cathepsin-L and papain and showed no inhibitory activity against a wide range of serine proteases [14], so it is perhaps more likely that leupin will also show inhibitory activity against a cysteine protease.…”

Section: Discussionmentioning

confidence: 99%

“…The gene encoding for SCCA has been cloned and sequenced from SKGIIIa cells, a uterine cervical carcinoma cell line [8]. The cleavage site of SCCA is Se~Ser which is unique to this serpin, and the protein has recently been shown to have inhibitory activity against cathepsin L and papain which are cysteine rather than serine proteases [14]. This cross-class inhibitory activity has previously been seen in the viral serpin crmA which inhibits the cysteine protease interleukin-1 fl-converting enzyme (ICE) [15,16].…”

Section: Introductionmentioning

confidence: 99%

Identification of a novel human serpin gene; cloning sequencing and expression of leupin

Barnes

Worrall

1995

FEBS Letters

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“…proteinases [3][4][5][6]. In addition, the ability of the plasma serpin inhibitor of coagulation proteinases, antithrombin, to inactivate the plant cysteine proteinase, papain, and the bacterial cysteine proteinase, Arg-gingipain, has been reported [7,8].…”

Section: Introductionmentioning

confidence: 99%

Inactivation of papain by antithrombin due to autolytic digestion: a model of serpin inactivation of cysteine proteinases

Björk

Nordling

Raub-Segall

et al. 1998

Biochemical Journal

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Cross-class inhibition of cysteine proteinases by serpins differs from serpin inhibition of serine proteinases primarily in that no stable serpin-cysteine proteinase complex can be demonstrated. This difference in reaction mechanism was elucidated by studies of the inactivation of the cysteine proteinases, papain and cathepsin L, by the serpin antithrombin. The two proteinases were inactivated with second-order rate constants of (1.6p0.1) i10$ and (8.6p0.4)i10# M −"

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Squamous cell carcinoma antigen is a potent inhibitor of cysteine proteinase cathepsin L

Cited by 55 publications

References 23 publications

A New Family of 10 Murine Ovalbumin Serpins Includes Two Homologs of Proteinase Inhibitor 8 and Two Homologs of the Granzyme B Inhibitor (Proteinase Inhibitor 9)

A New Family of 10 Murine Ovalbumin Serpins Includes Two Homologs of Proteinase Inhibitor 8 and Two Homologs of the Granzyme B Inhibitor (Proteinase Inhibitor 9)

Identification of a novel human serpin gene; cloning sequencing and expression of leupin

Inactivation of papain by antithrombin due to autolytic digestion: a model of serpin inactivation of cysteine proteinases

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