Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we established hepatitis C virus (HCV) core-expressing mouse liver cells and investigated changes occurring in the gene expression profile accompanied by expression of the viral core protein using DNA array analysis. Both non-transformed and transformed mouse liver cells constitutively expressing the viral core protein were established by DNA transfection, and subjected to DNA array analysis. For the genes judged positive by DNA array, Northern blot analysis was done for corroboration. DNA array analysis revealed one up-regulated gene and three down-regulated genes by expression of the viral core protein in non-transformed liver cells. For the transformed liver cells, four enhanced and five suppressed genes were observed. The Northern blot corroboration analysis clarified two genes, osteopontin precursor and activating transcription factor 4, as being down-regulated by the viral core protein in both non-transformed and transformed liver cells, and three genes, cathepsin D, matrix metalloproteinase 14 and anti-proliferative B-cell translocation gene 2, as being up-regulated by the viral core protein in only transformed liver cells. In conclusion, a total of five genes were identified as viral core protein-responsive ones in the DNA array analysis. Alterations in the expression levels of these genes may be relevant to the viral core-mediated pathogenesis.
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PMID:Changes in gene expression profile by HCV core protein in cultured liver cells: analysis by DNA array assay. 1269 50

Recent studies demonstrate that presenilins (PSs) and signal peptide peptidase (SPP) are members of a novel protease family of integral membrane proteins that may utilize a catalytic mechanism similar to classic aspartic proteases such as pepsin, renin and cathepsin D. The defining features of the PSs and SPP are their ability to cleave substrate polypeptides within a transmembrane region, the presence of two active site aspartate residues in adjacent membrane-spanning regions and a conserved PAL motif near their COOH-terminus. PSs appear to be the catalytic subunit of multiprotein complexes that possess gamma-secretase activity. Because this activity generates the amyloid beta peptide (Abeta) deposited in the brain of patients with Alzheimer's disease (AD), PSs are considered therapeutic targets in AD. In contrast to PSs that are not active unless part of a larger complex, SPP does not appear to require protein co-factors. Because of its requirement for hepatitis C virus maturation and a possible immune modulatory role, SPP is also considered a potential therapeutic target. Four additional PS/SPP homologs have been identified in humans; yet, their functions have not been elucidated. Herein, we will review the recent advances in our understanding of the PS/SPP family of proteases as well as discuss aspects of intramembrane cleavage that are not well understood.
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PMID:Intramembrane-cleaving aspartic proteases and disease: presenilins, signal peptide peptidase and their homologs. 1296 28

Activity-based protein profiling (ABPP) offers direct insight into changes in catalytic activity of enzyme classes in complex proteomes, rather than protein or transcript abundance. Here, ABPP was performed in Huh7 hepatoma cell lines with a group of ABPP probes composed of an N-acetylated amino acid, that mimic the P(1) position in protease peptide substrates. Five different probes bearing distinct amino acids (Ser, Thr, Phe, Glu and His) labeled 54 differentially active proteins, including proteases, other hydrolases, oxidoreductases and isomerases. Four of the six protease families were targeted based on their P(1) substrate preferences. The broader specificity of the labeling observed could be explained by the substrate-based targeting nature and the electrophilic properties of the ABPP probes. When applied to Huh7 cells stably replicating hepatitis C virus (HCV) subgenomic replicon RNA, four proteins showed reduced activity, while three proteins had increased activity during HCV replication. These differentially active hits included carboxylesterase 1, cathepsin D, HSP105, protein disulfide isomerase 1 and A6, chaperonin containing TCP1 and isochorismatase domain containing 1, which demonstrated substrate preferences by being labeled by specific substrate probes. This illustrates the broader activity-based profiling capabilities of these substrate-based probes to reveal novel enzyme candidates and their potential roles during HCV replication.
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PMID:Activity-based proteome profiling of hepatoma cells during hepatitis C virus replication using protease substrate probes. 1995 26