Disease relevance of Ctrl

• Expulsion of gastrointestinal nematodes is associated with pronounced mucosal mast cell (MMC) hyperplasia, differentiation, and activation, accompanied by the systemic release of MMC granule chymases (chymotrypsin-like serine proteases) [1].
• The ATP-ubiquitin-dependent proteolytic pathway is considered to play a major role in muscle catabolism in cachexia, and functional proteasome activity, as determined by "chymotrypsin-like" enzyme activity, was significantly elevated in gastrocnemius muscle of mice bearing the MAC16 tumor as weight loss progressed [2].
• Muscle atrophy after 4 d of high-dose dexamethasone was associated with increased mRNA of enzymes involved in proteolytic pathways (atrogin-1, muscle ring finger 1, and cathepsin L) and increased chymotrypsin-like proteasomal activity [3].
• The coronavirus, mouse hepatitis virus strain A59 (MHV), expresses a chymotrypsin-like cysteine proteinase (3CLpro) within the gene 1 polyprotein [4].
• Sindbis virus multicycle replication in cultured cells was suppressed by N-tosyl-phenylalanine chloromethyl ketone (TPCK), an inhibitor of chymotrypsin-like proteinases, and by aprotinin, an inhibitor of a wide spectrum of proteinases [5].

High impact information on Ctrl

• Three distinct peptidase activities of this enzyme complex (trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolyzing activities) were inhibited by lactacystin, the first two irreversibly and all at different rates [6].
• IFN-gamma stimulation results in a downregulation of the chymotrypsin-like Suc-LLVY-MCA peptide hydrolyzing activity of 20S proteasomes whereas the trypsin-like activity remains unaffected [7].
• When tested as a substrate a synthetic 25-mer polypeptide whose sequence covers the antigenic nonapeptide YPHFMPTNL of the MCMV pp89, 20S proteasomes of IFN-gamma-induced cells exhibit altered chymotrypsin-like cleavage site preferences [7].
• RESULTS: VSL#3 produces soluble factors that inhibit the chymotrypsin-like activity of the proteasome in gut epithelial cells [8].
• Although halomethyl ketone derivatives of phenylalanine were originally designed and used for affinity labeling of the active site of chymotrypsin and similar enzymes, no evidence was found for a chymotrypsin-like activity of interferons [9].

Chemical compound and disease context of Ctrl

• Induction of various androgen-dependent esteroproteases (trypsin-like and chymotrypsin-like enzymes) by tri-iodo-L-thyronine in the submandibular glands of female mice and mice with testicular feminization [10].

Biological context of Ctrl

• The enzyme was shown to be controlled by the presumed structural locus Ctra-1 located on chromosome 8 [11].
• Using primary hepatocytes, we found that TGF-beta-induced G1 arrest, apoptosis, and epithelial-to-mesenchymal transition in Ctrl and S2HeKO but not in S3KO hepatocytes [12].
• The serine protease showed chymotrypsin-like substrate specificity [13].
• Degradation of the catalytic subunit in kinase-negative, but not in wild-type, cells was inhibited strongly by two specific peptide aldehyde inhibitors of the proteasomal chymotrypsin-like activity [14].
• ORF 1a, which encodes a protein of 242.8 kDa and is located at the 5' end of the genome, contains at least two putative papain-like cysteine protease domains, and one putative chymotrypsin-like serine protease domain [15].

Anatomical context of Ctrl

• A 334+/-44% increase (P<0.001 versus Ctrl) in relative retention of (111)In-RP782 was confirmed by gamma well counting of myocardium [16].
• Subsequent to target cell binding, but prior to programming for lysis by Ca2+, NK cell lytic activity could be suppressed by inhibitors of chymotrypsin-like, but not trypsin-like proteases, in contrast to CTL [17].
• Subunit rLMP7 of the multicatalytic proteinase (MCP), which has been associated with chymotrypsin-like proteinase activity, was examined in rat liver and hepatocyte-derived cell lines. rLMP7 was detected in both nucleus and cytosol in liver by immunohistochemistry and immunoblotting, using a peptide-specific anti-rLMP7 antibody [18].
• Both agents completely attenuated total protein degradation in murine myotubes at all concentrations of PIF, and attenuated the PIF-induced increase in expression of the ubiquitin-proteasome proteolytic pathway, as determined by the 'chymotrypsin-like' enzyme activity, proteasome subunits and E2(14k) [19].
• In both myoblasts and myotubes protein degradation was accompanied by an increased expression of the alpha-type subunits of the 20S proteasome as well as functional activity of the proteasome, as determined by the 'chymotrypsin-like' enzyme activity [20].

Associations of Ctrl with chemical compounds

• Tumor-bearing mice were divided into 12 groups [Control (Ctrl), DOX, SeMET, SeMET + DOX, Ad-Ctrl, Ad-Ctrl + SeMET, Ad-Ctrl + DOX, Ad-Ctrl + SeMET + DOX, Ad-MET, Ad-MET + DOX, Ad-MET + SeMET, and Ad-MET + SeMET + DOX] [21].
• Crude and purified proteasome preparations were exposed to PN or to the PN donor, 3-morpholinosydnonimine hydrochloride (SIN-1), and then assayed for chymotrypsin-like activity [22].
• Other enzymes represented, but at lower levels, included elastase IV, proteinase 3, complement C2, chymotrypsin B, chymotrypsin-like protein, and Hageman factor [23].
• The chymotrypsin-like but not the trypsin-like activity of the proteasome is required for the infection, since the chymotrypsin inhibitors N-tosyl-L-phenylalanine chloromethyl ketone and aclarubicin were both effective in blocking MVMp infection [24].
• N-Acetyl-L-tyrosine ethyl ester (ATEE) and N-benzoyl-L-arginine ethyl ester (BAEE) are reversible substrate inhibitors of proteinases with trypsin-like and chymotrypsin-like specificities, respectively [25].

Regulatory relationships of Ctrl

• These studies suggest that specific inhibition of the chymotrypsin-like activity of the proteasome is sufficient to prevent signal-induced NF-kappa B activation and that the proteasome is a novel target for the identification of agents that may be useful in the treatment of diseases whose etiology is dependent upon the activation of NF-kappa B [26].
• Cloning and characterization of mouse klk27, a novel tissue kallikrein expressed in testicular Leydig cells and exhibiting chymotrypsin-like specificity [27].

Other interactions of Ctrl

• Functionally, LPS enhanced the chymotrypsin-like activity of the proteasome to degrade synthetic peptides in vitro and, conversely, the proteasome inhibitor lactacystin completely blocked the LPS-induced proteasome's chymotrypsin activity as well as macrophage TNF-alpha secretion and the expression of multiple inflammatory mediator genes [28].
• Active recombinant mKlk27 exhibited chymotrypsin-like cleavage specificity [27].
• A novel chymotrypsin-like proteinase termed myonase was previously purified from MDX-mouse skeletal muscle [Hori et al. (1998) J. Biochem. 123, 650-658] [29].
• The PIF-induced increase in chymotrypsin-like enzyme activity was also attenuated by the NF-kappaB inhibitor peptide SN50, suggesting that NF-kappaB may be involved in the PIF-induced increase in proteasome expression [30].
• CCP2 exhibits chymotrypsin-like activity while HF displays trypsin-like activity [31].

Analytical, diagnostic and therapeutic context of Ctrl

• Furthermore, WA potently inhibits the chymotrypsin-like activity of a purified rabbit 20S proteasome (IC50=4.5 microM) and 26S proteasome in human prostate cancer cultures (at 5-10 microM) and xenografts (4-8 mg/kg/day) [32].
• While LMF had no effect on the lysosomal enzymes, cathepsins B and L, there was a decrease in proteasome activity, as determined both by the 'chymotrypsin-like' enzyme activity, as well as expression of proteasome alpha-type subunits, determined by Western blotting [33].
• Trypsin-like and chymotrypsin-like esteroprotease isozymes of the mouse submandibular gland were separated by isoelectric focusing [10].
• Basic isozymes of chymotrypsin-like esteroprotease from mouse submandibular glands were purified 60-80-fold by a rather simple procedure consisting of CM-Sepharose CL6B chromatography and gel filtration on Sephadex G-100 [34].

References