Figure 2.

(a) Structure of the constitutive proteasome (cP) and the immunoproteasome (iP). Following stimulation with pro-inflammatory cytokines, the immunosubunits (β1i, β2i, and β5i) are preferentially incorporated into proteasomes to the detriment of the constitutive ones (β1, β2, β5). The iP is constitutively expressed in cells of hematopoietic origin under normal conditions. Independently of INF-γ-induced iP expression, expression of the regulatory particle PA28 is also upregulated by INF-γ and can bind to one or both ends of the 20S core particle of the cP or the iP with the same affinity. (b) Inhibitors of the proteasome can be designed to target both cPs and iPs or to selectively target the iP.