A PROTEASOME ACTIVATOR SUBUNIT BINDS CALCIUM

We recently cloned a cDNA encoding the 29-kDa subunit of human red blo od cell regulator (REG), a potent activator of the multicatalytic prot ease (Realini, C., Dubiel, W., Pratt, G., Ferrell, K., and Rechsteiner , M. (1994) J. Biol. Chem. 269, 20727-20732). The sequence of this sub unit contains 28 ''alternating'' lysine and glutamic acid residues (a KERE motif), Similar regions are present in a number of Ca2+-binding p roteins, and using standard filter assays, the recombinant protein is shown to bind Ca-45(2+) and ruthenium red, Ca-45(2+) is also bound to a ubiquitin extension protein containing the 28-residue KEKE region fr om the 29-bDa REG subunit, Thus, the 29-kDa REG subunit is a Ca2+-bind ing protein, and its KEKE region is able to bind divalent cations, Ca2 + reversibly inhibits the enhanced peptidase activity of complexes bet ween the multicatalytic protease and recombinant REG, This raises the possibility that multicatalytic protease activity is regulated by calc ium in vivo.