ABSTRACT

Proteasomes, the world of regulatory proteolysis: surprise and astonishment has struck the scientific community when the structural complexity and principal functions of these large proteinase particles became apparent. From degradation of malfolded proteins, antigen generation, regulatory adaptation, to control of cell cycle: the functions of proteasomes are numerous, and many surprises may lie still ahead of us. For a long time researchers had resented the idea that proteinases could be involved in cellular regulation. This was due to the fact that it was hard to imagine at the time that vital macromolecular constituents, which are synthesized at the expense of a lot of energy, should be destroyed again. From the time on that we know that regulation within a cell is most important for survival and the more fine tuned regulation is, the more energy it consumes, proteolysis was not any more the unthinkable in regulation. The beauty of proteolysis rests in the speed with which regulation can proceed and in the irreversibility of the reaction. However, the intracellular proteinases found were mostly of lysosomal origin and rather highly unspecific. Thus, the lysosome was considered the gut of the cell which by virtue of its unspecific proteinases digested unnecessary proteins and protein garbage. As a delivery mechanism of proteins to the lysosomal proteolytic m achinery autophagocytosis had been found (see for instance 1,2). However, as the autophagic-

lysosomal pathway of protein degradation is a nonselective bulk process,1 it was hard to imagine how such a process could be respon­ sible for selective protein degradation, a prerequisite for fine tuned cellular regulation.