Investigation of the ubiquitin-specific protease UBP41 and of the lysosomal cysteine proteases cathepsin-L and cathepsin-B as potential mediators of proapoptotic signalling

Two projects are described within the scope of this thesis. The
first project characterizes the ubiquitin-specific protease UBP41
as a protein which upon overexpression causes apoptosis induction
in several mammalian cancer cell lines. The second project
investigates a possible involvement of the lysosomal cysteine
proteases cathepsin-L and cathepsin-B in apoptosis pathways induced
by distinct death stimuli, in particular by the tumor necrosis
factor a (TNF-a). Therefore, both projects examine a possible
regulation of apoptosis induction by proteases that are part of one
of the two major systems of protein degradation. UBP41 as a
protease with deubiquitylating activity is expected to play a role
in the ubiquitin/proteasome system which is the major proteolytic
apparatus for the degradation of cytosolic proteins. Cathepsins, on
the other hand, are lysosomal proteases that participate in the
breakdown of membrane-associated proteins and of extracellular
proteins that are taken up by endocytosis. Both, the
ubiquitin/proteasome system as well as lysosomal proteases have
been previously implicated in the regulation and mediation of
apoptosis, and it therefore appeared particularly attractive to
further study the effect of UBP41 and cathepsins on cell death
signalling in more detail.