A 220-kDa activator complex of the 26 S proteasome in insects and humans -A role in type II programmed insect muscle cell death and cross-activationof proteasomes from different species

The S10b (SUG2) ATPase cDNA has been cloned by reverse transcription-polyme rase chain reaction/rapid amplification of cDNA ends from mRNA of intersegm ental muscles of the tobacco horn moth (Manduca sexta), The S10b ATPase is a component of the 26 S proteasome, and its concentration and that of its m RNA increase dramatically during development in a manner similar to other A TPases of the 19 S regulator of the 26 S proteasome. The S10b and S6' (TBP1 ) ATPases are also present in a complex of similar to 220 kDa in intersegme ntal muscles. The 220-kDa complex markedly activates (2-10-fold) the 26 S p roteasome, even when bound to anti-S10b antibodies immobilized on Sepharose , and increases in concentration similar to 5-fold like the 26 S proteasome in the intersegmental muscles in preparation for the programmed death of t he muscle cells. A similar activator complex is present in human brain and placenta. Free activator complexes cross-activate: the Manduca complex acti vates rat skeletal muscle 26 S proteasomes, and the placental complex activ ates Manduca 26 S proteasomes. The placental activator complex contains S10 b and S6', but not p27, This 220-kDa activator complex has been evolutionar ily conserved between species from insect to man and may have a fundamental role in proteasome regulation.