Ubiquitin-mediated proteolysis provides an important mechanism for reg
ulating a variety of cellular processes. Ubiquitin-conjugated proteins
are degraded by a 26 S protease that contains more than 30 different
subunits. Of these, a single 50-kDa polypeptide, subunit 5, specifical
ly binds ubiquitin-lysozyme conjugates. Binding is inhibited by short
polymeric chains of ubiquitin but not by ubiquitin monomers or by lyso
zyme. In addition, subunit 5 binds free ubiquitin chains with efficien
t association requiring at least four ubiquitins. Thus, proteins conju
gated to polymers of ubiquitin may be selected for degradation by a si
ngle subunit of the 26 S protease complex.