Disease relevance of Csta_predicted

• Inhibition of growth and cysteine proteinase activity of Staphylococcus aureus V8 by phosphorylated cystatin alpha in skin cornified envelope [1].
• Cystatin alpha was purified from Escherichia coli transfected with a recombinant cystatin alpha gene and injected into the tail vein of rats [2].
• The inhibitory properties of phosphorylated cystatin alpha (P-cystatin alpha) and a conjugated protein of the P-cystatin alpha with filaggrin linker segment peptide (FLSP) against the growth of Staphylococcus bacteria and poliovirus were investigated [3].
• Cystatin A expression reduces bile salt-induced apoptosis in a rat hepatoma cell line [4].

High impact information on Csta_predicted

• Lysine-rich phosphorylated cystatin alpha (P-cystatin alpha) from newborn rat epidermis is a good substrate for epidermal transglutaminase (TGase) and also one of the component proteins of cornified envelope in the stratum corneum [5].
• Serum calcium in rats placed on a low calcium diet was decreased by treatment of E-64 or cystatin A, but not by CA-074 [6].
• Thus phosphorylation of cystatin alpha by protein kinase C may play an important role in targeting cystatin alpha into KHG [7].
• Treatment of sphingosine, a specific inhibitor of protein kinase C, markedly suppressed the incorporation of cystatin alpha into KHG [7].
• The incorporation increased dose-dependently with the added cystatin alpha and was inhibited significantly by H-7, a specific inhibitor of PKC [8].

Biological context of Csta_predicted

• Amino acid sequence of rat epidermal thiol proteinase inhibitor [9].
• Therefore, it is highly possible that the HSP is a phosphorylated cystatin alpha and that the phosphorylation is catalyzed specifically by PKC [8].
• This suggests that the conserved Val in the reactive site is not restricted and that the hydrophobicity of the position is not essential for the activity of rat cystatin A [10].

Anatomical context of Csta_predicted

• Incorporation and degradation by kidney lysosomes of cystatin alpha injected intravenously [2].
• The cystatin alpha gene was inserted into an inducible expression vector, pMSG, and transfected into NIH3T3 mouse fibroblasts [11].

Associations of Csta_predicted with chemical compounds

• Evidence of protease activity producing NH2-terminal truncated form of rat cystatin A in newborn rat epidermis [12].
• The pI 4.7, 14.5 kDa hematoxylin-stainable protein (HSP) from rat epidermis inhibited the activities of the cysteine proteinases papain, ficin, cathepsins B, H and L with similar inhibitory characteristics as recombinant cystatin-alpha [13].
• When phosphorylated cystatin alpha (P-cystatin alpha) was incubated with epidermal transglutaminase (TGase) and Ca2+ ions, polymerized protein was produced by formation of epsilon-(gamma-glutamyl)lysine cross-linking peptide bonds between lysine residues of cystatin alpha and glutamine residues of suitable protein(s) in the enzyme preparation [7].
• Furthermore, 32P from [gamma-32P]ATP was incorporated into recombinant cystatin alpha by a protein kinase C (PKC) preparation in the presence of phosphatidyl serine and Ca2+ ions as co-factors [8].
• The inactivation and degradation of L-lactate dehydrogenase by this partially purified enzyme were all markedly suppressed by a low level of cystatin alpha without inhibiting the activities of both cathepsins B and L [14].

Regulatory relationships of Csta_predicted

• Expression of cystatin A was used to inhibit cathepsin B, whereas Z-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK) was used to inhibit caspases [4].

Other interactions of Csta_predicted

• Phosphorylated cystatin alpha is a natural substrate of epidermal transglutaminase for formation of skin cornified envelope [7].
• The activity of cathepsin H in the kidney lysosomal fraction was markedly decreased 30 min after injection of cystatin alpha but recovered rapidly [2].
• Cystatin A expression prevented cathepsin B activation and apoptosis during treatment with glycochenodeoxycholate (GCDC), a toxic bile salt [4].

Analytical, diagnostic and therapeutic context of Csta_predicted

• Epidermal thiol proteinase inhibitor (EPI) was extracted from normal and psoriatic cornified cells with 10 mM Tris-HCl, pH 8.0, and purified by papain-Sepharose affinity chromatography and gel filtration [15].
• The in vivo location of both HSP and cystatin-alpha is on keratohyalin granules in epidermis as detected by indirect immunofluorescence technique using individual antibodies [13].
• SDS-PAGE autoradiography of the 32P-labeled proteins showed that 32P was incorporated into the cystatin alpha [8].
• Its fate was then followed using a sensitive enzyme immunoassay for cystatin alpha [2].
• The high molecular weight protein enzymatically synthesized from phosphorylated cystatin alpha and FLSP by TGase reacted with both anti-FLSP/KLH antibody and anti-P-cystatin alpha antibody on Western blotting [16].

References