PRIMARY STRUCTURES OF 2 HOMOLOGOUS SUBUNITS OF PA28, A GAMMA-INTERFERON-INDUCIBLE PROTEIN ACTIVATOR OF THE 20S PROTEASOME

The primary structures of two proteins that comprise PA28, an activato r of the 20S proteasome, have been determined by cDNA cloning and sequ encing, These protein subunits, termed PA28 alpha and PA28 beta, are a bout 50% identical to one another and are highly conserved between rat and human, PA28 alpha and PA28 beta are homologous to a previously de scribed protein, Ki antigen, whose function is unknown, PA28 alpha, bu t neither PA28 beta nor Ki antigen, contains a 'KEKE motif', which has been postulated to promote the binding of proteins having this struct ural feature, PA28 alpha and PA28 beta were coordinately regulated by gamma-interferon, which greatly induced mRNA levels of both proteins i n cultured cells, The mRNA level of the Ki antigen also increased in r esponse to gamma-interferon treatment, but the magnitude of the increa se was less than that for the PA28s, and the effect was transient, The se results demonstrate the existence of a new protein family, at least two of whose members are involved in proteasome activation, They also provide the basis for future structure/function studies of PA28 subun its and the determination of their relative physiological roles in the regulation of proteasome activity.