In eukaryotes, ubiquitin-mediated
proteolysis (UMP) is the main pathway for selective degradation of
short-lived proteins. These include many regulators with diverse
functions in cell biology, e.g. cyclins, Cdk inhibitors and
transcriptional activators or repressors as Gcn4p or Matalpha2p.
Substrates that are marked for degradation by the attachment of multi-ubiquitin chains are degraded by the 26S proteasome. It is composed of a
catalytic core, the 20S proteasome, and two 19S regulators that are
specifically required for the degradation of ubiquitylated proteins. We
have isolated several mutants, ump1-ump5 , with defects in this
pathway. These mutants directly affect the function of the proteasome.
The UMP1 gene was found to be required for proper maturation of
the proteasome (Ramos et al., Cell 92, 489-499). Ump1p is a short-lived
chaperone present in half-proteasome precursors characterized by the
presence of unprocessed beta-subunits. Upon formation of the 20S
particle from these precursors, Ump1p becomes encased and assists in
activation of the protease (processing of beta-subunits). Ump1p is
degraded after activation of the proteolytic sites making it the first
substrate of the newly formed proteasome. The ump2 and
ump4 mutations were localized to genes encoding 20S proteasome
subunits. Our analyses revealed that both mutants are deficient in beta-subunit processing, and suggested a defined order of processing
events.
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