Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal errors and cell death

Antonio Baici, Kathrin Müntener, Anna Willimann, Roman Zwicky
2006 Biological chemistry  
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
more » ... tochondria. 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.
doi:10.1515/bc.2006.125 pmid:16895470 fatcat:cpecfembyjglnb3gqiqria3lca