ライフサイエンスコーパス: cathepsin S

1 the substrate-binding subsites S3 to S1' of cathepsin S.

2 l intermolecular contacts that are unique to cathepsin S.

3 involves endocytic compartments enriched in cathepsin S.

4 gamma inducing factor, apolipoprotein E, and cathepsin S.

5 d fibroblasts expressed detectable levels of cathepsin S.

6 atment with a variety of proteases including cathepsin S.

7 cathepsin L, but distinctly less stable than cathepsin S.

8 eavage, most likely by the cysteine protease cathepsin S.

9 an evolutionarily related cysteine protease, cathepsin S.

10 activity of the lysosomal cysteine protease, cathepsin S.

11 designed to explore the S3 binding pocket of cathepsin S.

12 gned to target the homologous human protease cathepsin S.

13 rovided inhibitors with moderate potency for cathepsin S.

14 dehyde inhibitors with nanomolar affinity to cathepsin S.

15 staining for the powerful elastolytic enzyme cathepsin S.

16 A1, A2, and A3 (Stfa1-Stfa3), inhibitors of cathepsin S, a cysteine protease required for autoantige

17 Cathepsin S, a lysosomal cysteine protease of the papain

18 We show that the cysteine protease cathepsin S activates MrgprC11 and evokes receptor-depen

19 nscriptional mediator of IFN-gamma-dependent cathepsin S activation.

20 highly potent cathepsin K inhibitor but with cathepsin S activity and very poor stability to microsom

21 of Ii, revealing MHC class II haplotype and cathepsin S activity as regulators of NK T cells.

22 or the existence of specific localization of cathepsin S activity in dendritic cells.

23 lls from IRF-1(-/-) mice fail to up-regulate cathepsin S activity in response to IFN-gamma.

24 e demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues.

25 Cathepsin S activity is essential for complete processin

26 Unique among cysteine proteases, cathepsin S activity is up-regulated by IFN-gamma.

27 Cs, inefficient Ii chain cleavage due to low cathepsin S activity leads to the transport of class II-

28 to lysosomes, while in mature DCs, elevated cathepsin S activity results in efficient delivery of cl

29 Interestingly, cathepsin S activity was strongly up-regulated in sample

30 d identified vesicles containing exclusively cathepsin S activity.

31 ation of HLA-DR was not explained by altered cathepsin S activity.

32 Here, we show that the cysteine protease cathepsin S acts in a concerted fashion with other cyste

33 Furthermore, cathepsin S affected the production of type IV collagen-

34 In the structure of the cathepsin S-aldehyde complex, the tetrahedral thiohemiac

35 athepsin S inhibition and a null mutation of cathepsin S also decreased IFN-gamma-induced DNA injury,

36 anscription-PCR showed a >4-fold increase in cathepsin S, an enzyme important in antigen presentation

37 l forms (1.5 and 1.9 A) of a complex between cathepsin S and a triazole inhibitor incorporating a chl

38 okines IL-1beta or IFN-gamma secreted active cathepsin S and degraded substantial insoluble elastin (

39 )-22 proved to be potent inhibitors of human cathepsin S and exhibited notable selectivity over human

40 ose the X-ray structure of a complex between cathepsin S and inhibitor 2 which reveals an unprecedent

41 using dramatic build-up of the p8 product of Cathepsin S and interfering with earlier steps in CD74 e

42 ins crucial for antigen presentation, namely cathepsin S and invariant chain, was determined.

43 ze allergen and expressed marginal levels of cathepsin S and invariant chain.

44 ases (MMP-2, MMP-9), cysteine endoproteases (cathepsin S and K), and interleukin-1beta, a cytokine th

45 I and IL6, lesion matrix-degrading proteases cathepsin S and matrix metalloproteinase-9, and systemic

46 Cathepsin S and TGF-beta1 were elevated more than 15-fol

47 in a reaction in which the cysteine protease cathepsin S and the accessory molecule H-2DM play an ess

48 e MHC class II endosomal processing pathway, cathepsin S and the invariant chain, in the normal funct

49 -Le(X) neither required TAP-transporters nor Cathepsin-S and was still observed after prolonged intra

50 sin-deficient B cells to examine the role of cathepsins S and B in the degradation of other molecules

51 tantly, the levels of IL-18 and its targets, cathepsins S and B, were increased in pulmonary macropha

52 Cathepsins S and K are potent mammalian proteases secret

53 mined the expression of the potent elastases cathepsins S and K in human atheroma.

54 Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arteri

55 ver, macrophages from mice deficient in both cathepsins S and L can process Ii and load peptides onto

56 s of specific cysteine proteases, especially cathepsins S and L, in degrading the invariant chain and

57 eine protease with high sequence homology to cathepsins S and L, members of the papain superfamily of

58 as found to be intermediate between those of cathepsins S and L.

59 ization of cathepsin K is similar to that of cathepsins S and L.

60 n K, a novel cysteine protease homologous to cathepsins S and L; ESTs for other cathepsins were rare.

61 hree subunits of complement C1q, lysozyme M, cathepsins S and Z, cytochrome b558 small subunit, macro

62 tivity/protein of the elastolytic proteases, cathepsin S, and metalloproteinase-9.

63 herosclerotic mediators, like Calgranulin A, Cathepsin S, and Osteopontin.

64 three CJD models, the upregulation of CCR5, cathepsin S, and TGF-beta1 was variable with respect to

65 mokine receptor CCR5, the lysosomal protease cathepsin S, and the pleiotropic cytokine transforming g

66 whereas glial fibrillary acidic protein and cathepsin S are up-regulated throughout the entire neoco

67 inflammatory plasma proteins, we identified cathepsin S as a lead indicator of liver disease.

68 Systemic inhibition of cathepsin S attenuates the progression of atheroscleroti

69 A selective inhibitor of cathepsin S blocked > 80% of this elastolytic activity.

70 cificity of human cathepsin O2 is similar to cathepsin S but distinguished from cathepsins L and B.

71 Purified cathepsin S, but not cathepsin B, H, or D, specifically

72 Inhibition of cathepsin S by HCV proteins increased cell surface expre

73 These genes are cathepsin S, C1q B-chain of complement (C1qB), beta2-mic

74 rved from hydrolysis when a 10-fold ratio of cathepsin S cannibalized the highly collagenolytic cathe

75 This study tested the hypothesis that cathepsin S (Cat S) contributes to angiogenesis.

76 f myasthenia gravis, we examined the role of cathepsin S (Cat S) in experimental autoimmune myastheni

77 overexpress the lysosomal cysteine protease cathepsin S (Cat S), one of the most potent mammalian el

78 e former use the lysosomal cysteine protease cathepsin S (Cat S), whereas thymic cortical epithelial

79 Cathepsin S (Cat-S) is a lysosomal cysteine protease of

80 zed a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades e

81 Similar to cathepsin S, cathepsin O2 is characterized by a bellshap

82 In contrast to cathepsin L, but similar to cathepsin S, cathepsin V exhibited only a very weak coll

83 Cathepsin S (CATS) and cathepsin H (CATH) activities wer

84 Cathepsin S (catS) and cathepsin L (catL) mediate late s

85 egradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal

86 covalent inhibitors of the cysteine protease cathepsin S (CatS) are described.

87 decreasing a proposed tear biomarker of SjS, cathepsin S (CATS) compared to free drug.

88 ce lacking the lysosomal cysteine proteinase cathepsin S (catS) demonstrated a profound inhibition of

89 We have dissected the role of cathepsin S (CatS) in the trafficking and maturation of

90 uated by prolonged intrathecal delivery of a cathepsin S (CatS) inhibitor and a fractalkine (FKN) neu

91 rocess that was blocked by chloroquine and a cathepsin S (CatS) inhibitor; brefeldin A (BFA) also blo

92 -phenyl (LHVS), an irreversible inhibitor of cathepsin S (CatS) whose proteolytic activity is also in

93 imaging to test the hypothesis in vivo that cathepsin S (catS), a potent elastolytic proteinase, acc

94 00-fold selective versus cathepsin B (CatB), cathepsin S (CatS), and trypsin-like as well as PGPH-lik

95 The potent protease cathepsin S cleaves elastin and generates bioactive elas

96 ve site loop and detection of a stable SCCA1-cathepsin S complex by sodium dodecyl sulfate-polyacryla

97 The t1/2 of SCCA1-cathepsin S complexes was >1155 min, whereas that of cys

98 al lysosomal proteases, cathepsin L (CL) and cathepsin S (CS), have been shown to process invariant c

99 Cathepsin S (CTSS) activity is increased in bronchoalveo

100 Cathepsin S (Ctss) is a cysteine protease that is active

101 Cathepsin S (CTSS) is a cysteine protease that is consti

102 1) repressed expression of the gene encoding cathepsin S (Ctss), a cysteine protease that cleaves inv

103 nt up-regulation of genes encoding proteases cathepsin S (CTSS), mast cell chymase (CMA1), tryptase (

104 arcinoma (HCC) cells preferentially secreted cathepsin S (CTSS), which regulates liver TICs through t

105 teraction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling.

106 accumulates within endocytic compartments of cathepsin S(-/-) DCs.

107 y implicated, we demonstrated that selective cathepsin S deficiency impaired angiogenesis and tumor c

108 Although cathepsin S-deficient mice have normal numbers of B and

109 Cathepsin S-deficient phagosomes generate a class I-pres

110 ity is further supported by the finding that cathepsin S degrades a number of extracellular matrix mo

111 These studies demonstrate that cathepsin S-dependent epithelial cell apoptosis is a cri

112 mma-Ser18, identified as the main product of cathepsin S-dependent IL-36gamma cleavage, induced psori

113 mples (P < 0.001), whereas the expression of cathepsin S did not significantly differ in these diseas

114 synthesized on solid support, incorporate a cathepsin S dipeptide substrate (Leu-Arg), and a poly(et

115 Upon proteolytic activation with cathepsin S (EC 3.4.22.27), CyPEG-2 showed greater than

116 is structural plasticity of the S2 pocket in cathepsin S explains the selective inhibition of catheps

117 ion of macrophage-like P388D cells and other cathepsin S-expressing cells.

118 CD4(+)HLA-DR(+) T cells down-regulated cathepsin S expression and activity 18 h after activatio

119 Furthermore, cathepsin S expression and activity, and concordantly ce

120 y, we examined the effect of HCV proteins on cathepsin S expression and found it to be markedly decre

121 Cathepsin S expression in macrophage-like synoviocytes s

122 In contrast, cathepsin S expression was restricted to CD68+ macrophag

123 ate the pathway by which IFN-gamma increases cathepsin S expression.

124 senting cells of mice that lack the protease cathepsin S fail to process Ii beyond a 10 kDa fragment,

125 Mice whose APC lack cathepsin S have reduced crosspriming to particulate and

126 ding, possibly by targeting ADAM10/17 and/or cathepsin S, have potential as peripheral approaches for

127 Increased cathepsin S immunofluorescence was detected in lysosomes

128 Specific inhibition of cathepsin S in A20 cells markedly impaired presentation

129 ased levels of precursor and mature forms of cathepsin S in agLDL-VSMC.

130 m laminin-5, revealing a functional role for cathepsin S in angiogenesis and neoplastic progression.

131 Specific inhibition of cathepsin S in B lymphoblastoid cells prevented complete

132 xes, whereas cathepsin F was as efficient as cathepsin S in CLIP generation.

133 hree-dimensional crystal structures of human cathepsin S in complex with potent covalent inhibitors,

134 Thus, the ratio of cystatin C to cathepsin S in developing DCs helps to determine the fat

135 ce in vivo selectively inhibited activity of cathepsin S in splenocytes, resulting in accumulation of

136 ture thiol reductase, but suggest a role for cathepsin S in the turnover of mature GILT and in regula

137 Thus, inhibition of cathepsin S in vivo alters Ii processing, antigen presen

138 Selective cathepsin S inhibition and a null mutation of cathepsin

139 We hypothesized that selective cathepsin S inhibition attenuates atherogenesis in hyper

140 here examine the functional significance of cathepsin S inhibition on antigen presentation and immun

141 expression and localization of an endogenous cathepsin S inhibitor cystatin C.

142 Furthermore, cathepsin S inhibitor or siRNA significantly decreased e

143 6.6 or 60 mg/kg of the potent and selective cathepsin S inhibitor RO5444101 or a control diet.

144 molecular weight (414 Da) and potent (15 nM) cathepsin S inhibitor that showed >1000-fold selectivity

145 lar weight (304 Daltons) and potent (9.6 nM) cathepsin S inhibitor that showed from 100- to >1000-fol

146 Administration of a cathepsin S inhibitor to mice in vivo selectively inhibi

147 e, modular synthesis of compound 1, a potent Cathepsin S inhibitor.

148 we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles.

149 Cathepsin S is a cysteine protease with potent endoprote

150 Cathepsin S is a lysosomal cysteine protease and control

151 These results indicate cathepsin S is a major Ii-processing enzyme in splenocyt

152 f a reversible inhibitor cocrystallized with Cathepsin S is also reported.

153 These data suggest that cathepsin S is an important player in degenerative disor

154 Thus, cathepsin S is essential in B cells for effective li pro

155 The cysteine protease cathepsin S is highly expressed in malignant tissues.

156 The cysteine protease cathepsin S is highly expressed in spleen, lymphocytes,

157 ely express class II MHC, we determined that cathepsin S is necessary for invariant chain proteolysis

158 Cathepsin S is not controlled transcriptionally but by a

159 Cathepsin S is one of the most important cysteine protei

160 pain cysteine protease superfamily including cathepsins S, L, and B and is selectively expressed in o

161 highly expressed selecively in osteoclasts; cathepsins S, L, and B were not detectable.

162 endritic cells lacking the cysteine protease cathepsin S lack the TAP-independent pathway.

163 els of the inflammatory markers lysozyme and cathepsin S may enable detection of multiple distinct st

164 activation of IL-36gamma and highlight that cathepsin S-mediated activation of IL-36gamma may be imp

165 f conventional protease-activated receptors, cathepsin S-mediated activation of MrgprC11 did not invo

166 suggested that HCV has an inhibitory role on cathepsin S-mediated major histocompatibility complex (M

167 dicate that differences in susceptibility to cathepsin S-mediated sigma3 processing are responsible f

168 acid-independent lysosomal cysteine protease cathepsin S mediates outer capsid processing in macropha

169 The cysteine endoprotease, cathepsin S, mediates Ii degradation in human and mouse

170 I-A(k), cathepsin S(-/-) mice do not accumulate class II-associa

171 In vitro, thymic dendritic cells (DCs) from cathepsin S(-/-) mice exhibit defective presentation of

172 stent with these data, we demonstrate, using cathepsin S(-/-) mice, that although the anti-PC respons

173 TNF-alpha induced cathepsin S, MMP-1, -3, and -9 mRNA expression in a dose

174 revealed that 10 ng/ml of TNF-alpha induced cathepsin S, MMP-1, -3, and -9 mRNA expression with the

175 Inhibition of cathepsin S molecules, blockade of costimulation through

176 l degeneration and reactive synaptogenesis), cathepsin S mRNA is dramatically increased in activated

177 dult rat brain, spleen, and lung reveal that cathepsin S mRNA is preferentially expressed in cells of

178 overexpression of IRF-1 increases endogenous cathepsin S mRNA levels in 293T epithelial cells.

179 s with increased levels of IRF-1 protein and cathepsin S mRNA.

180 the invariant chain (Ii) processing enzyme, cathepsin S, NK1.1(+) T cell selection and function are

181 Our data indicate that neither cathepsin S nor B is critical for H-2M degradation or pr

182 growth factor levels were also increased in cathepsin S-null mice.

183 igen presenting cells, and mice deficient in cathepsin S or cathepsin L exhibit severely impaired ant

184 s of bovine serum albumin generated by human cathepsin S or neutrophil elastase and into a fragment o

185 Cathepsins S or L are known to be required for the final

186 carcinoma tissue extracts did not change in cathepsin S- or cystatin C-null mice, tumor tissue basic

187 epsin S explains the selective inhibition of cathepsin S over cathepsin K afforded by inhibitors with

188 ased cleavage efficiency and selectivity for cathepsin S over cathepsins B, L, and K.

189 trated that RO5444101 reduced immunoreactive cathepsin S (P < 0.05), elastin degradation (P = 0.01),

190 The cysteine protease Cathepsin S performs a fundamental step in antigen prese

191 Therefore, cathepsin S plays a major role in generating presented p

192 de each other as well as the substrate, with cathepsin S predominantly degrading cathepsin K.

193 psin S-sufficient phagosomes and recombinant cathepsin S produce the mature epitope.

194 human vascular cells leads to an increase in cathepsin S production concomitantly with a decrease in

195 n of IRF-1, but not IRF-2, markedly augments cathepsin S promoter activity in A549 cells.

196 Our data demonstrate that the cathepsin S promoter contains an IFN-stimulated response

197 a specific fragment from the protease gene, cathepsin S (Rs-cps), was cloned into the binary vector

198 Among the cysteine proteases, cathepsin S seems to be best suited for such a process s

199 ization of the probe with CD68, elastin, and cathepsin S, similar to that observed in the experimenta

200 s with Lang virions were also inhibited by a cathepsin S-specific inhibitor.

201 In contrast, cathepsin S-sufficient phagosomes and recombinant cathep

202 of NH(4)Cl, cell lines engineered to express cathepsin S supported infection by Lang, but not c43, vi

203 ined expression of the elastinolytic enzyme, cathepsin S, the collagen metabolizing matrix metallopro

204 t, which is the binding affinity hot spot of cathepsin S, the Phe211 side chain can assume two stable

205 enzyme inhibitors, was previously applied to cathepsin S to obtain a novel (2-arylphenoxy)acetaldehyd

206 enzyme inhibitors, was previously applied to cathepsin S to obtain low nanomolar 1,4-disubstituted-1,

207 cidic protein, complement component C1q, and cathepsin S, up-regulation of which has been associated

208 eal time PCR and protein analyses identified cathepsin S, W, and C activity at sites of leukocyte pen

209 olecule inhibitors and siRNA gene silencing, cathepsin S was identified as the major IL-36gamma-activ

210 The downregulation of cathepsin S was mediated by HCV core and NS5A proteins i

211 eversible inhibitor of the cysteine protease cathepsin-S was prepared on large scale using a converge

212 of cathepsin F, the functional synergist of cathepsin S, was not observed.

213 Matrix metalloprotease 2 (MMP-2) and cathepsin S were present at baseline and were significan

214 -based probe (qABP) that selectively targets cathepsin S which is highly expressed in immune cells.

215 In contrast, cathepsin S, which does not form complexes with chondroi

216 uccessfully applied to the cysteine protease cathepsin S, which is implicated in autoimmune diseases.

217 nnover Functional Capacity Questionnaire and cathepsin S whose expression is limited to CD-68-positiv

218 CIITA-transfected astrocytes did not express cathepsin S without IFN-gamma activation, indicating tha