Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal errors and cell death
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Antonio Baici
Abstract
One of the control mechanisms of cathepsin B biosynthesis and trafficking operates through alternative splicing of pre-mRNA. An mRNA lacking exon 2 is more efficiently translated than that containing all exons, and may be responsible for elevated biosynthesis and enzyme routing to the extracellular space, with critical consequences for connective tissue integrity in pathologies such as cancer and arthritis. mRNA missing exons 2 and 3 encodes a truncated procathepsin B form that is targeted to mitochondria. This enzyme variant is catalytically inactive because it cannot properly fold. However, it provokes a cascade of events, which result first in morphological changes in intracellular organelles and the nucleus, finally leading to cell death.
References
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©2006 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Caspase-containing complexes in the regulation of cell death and inflammation
- Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal errors and cell death
- The peptidases from fungi and viruses
- C. elegans as a model system to study the function of the COG complex in animal development
- Functional responses of bone cells to thrombin
- Homologous substitution of ACE C-domain regions with N-domain sequences: effect on processing, shedding, and catalytic properties
- Production and processing of a recombinant Fasciola hepatica cathepsin B-like enzyme (FhcatB1) reveals potential processing mechanisms in the parasite
- Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata
- Single-cell resolution imaging of membrane-anchored hepatitis C virus NS3/4A protease activity
- Treatment of MCF-7 cells with taxol and etoposide induces distinct alterations in the expression of apoptosis-related genes BCL2, BCL2L12, BAX, CASPASE-9 and FAS
- Proteolytic mechanism of a novel mitochondrial and chloroplastic PreP peptidasome
- Tripeptidyl-peptidase I in health and disease
- Molecular and functional analysis of new members of the wheat PR4 gene family
- C-Terminal truncations of syncytin-1 (ERVWE1 envelope) that increase its fusogenicity
- Disease processes may be reflected by correlations among tissue kallikrein proteases but not with proteolytic factors uPA and PAI-1 in primary ovarian carcinoma
- Heparin modulation of human plasma kallikrein on different substrates and inhibitors
- Adaptation of the behaviour of an aspartic proteinase inhibitor by relocation of a lysine residue by one helical turn
- Cathepsins L and S are not required for activation of dipeptidyl peptidase I (cathepsin C) in mice