Immunoproteasomes are important for proteostasis in immune responses

Summary Immunoproteasomes are alternative forms of proteasomes that have an enhanced ability to generate antigenic peptides. Recently, Seifert and colleagues reported surprising observations concerning the functions of immunoproteasomes and cellular responses to interferon-γ: (1) that immunoproteasomes degrade ubiquitinated proteins faster than the constitutive proteasomes, (2) that polyubiquitin conjugates accumulate after interferon-γ treatment but then are preferentially degraded by immunoproteasomes, and (3) that immunoproteasome deficiency causes the formation of inclusions and more severe experimental autoimmune encephalomyelitis (EAE). In contrast, we find that polyubiquitin conjugates do not transiently accumulate following IFNγ-treatment and that immunoproteasomes do not prevent the formation of intracellular inclusions or protect against EAE. Furthermore, purified 26S constitutive and immunoproteasomes bind ubiquitin conjugates similarly and degrade them at similar rates. We conclude that, although immunoproteasomes can increase the generation of peptides appropriate for MHC class I presentation, they do not degrade ubiquitinated proteins more efficiently than constitutive particles.
Highlights ► IFNγ treatment does not cause an accumulation of ubiquitinated proteins in cells ► Immuno- and constitutive proteasomes degrade ubiquitin conjugates at similar rates ► Immunoproteasomes do not prevent the formation of intracellular inclusions ► LMP7 null mice do not develop more severe experimental autoimmune encephalomyelitis
New studies challenge a previously published conclusion that immunoproteasomes degrade ubiquitinated proteins more rapidly than conventional proteasomes.