REGULATORY PROTEINS OF THE PROTEASOME

The function of the proteasome is controlled by a variety of specific regulatory proteins including activators, inhibitors, and modulators. Two recently discovered activators, termed PA28 and PA700, bind to the terminal rings of the proteasome to form proteasome-regulator complexes which display greatly increased proteolytic activity. PA28 is a high-affinity activator of the proteasome's multiple peptidase activities. The carboxyl terminus of PA28 is required for its binding to the proteasome. PA700 binds to the proteasome via an ATP-dependent mechanism. PA700 has ATPase activity, and at least four of PA700's 16 subunits are members of a protein family containing a concensus sequence for ATP binding. Proteasome-PA700 complexes are activated with respect to both the hydrolysis of peptide substrates and the hydrolysis of ubiquitinated proteins.