Question

What is the role of cytokines in the formation of immunoproteasome?

Answer 1

The part of the proteasome which is involved in the regulation of innate immunity and inflammation, the Immunoproteasome is derived from the constitutive proteasome and is able to generate antigenic peptides. they are involved in immune responses against viral infections as they process viral proteins for antigen presentation. The constitutive proteasome has 6 parts, 2 inner beta rings, 2 outer alpha rings, and 2 regulatory 19S caps. there are different subunits to each of these ring structures which form the subunits of the constitutive proteasome.

cytokines such as interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) , induces the expression of immunoproteasome under inflammatory conditions such as infections and autoimmune disorders.

immunoproteasomes differ in five subunits from the constitutive proteasome:

iβ1 [large multifunctional peptidase 2 (LMP2 ), also called proteasome subunit beta type 9 (PSMB9)] replaces β1 of the inner β rings,

iβ2 [LMP10, multicatalytic endopeptidase complex-like-1 (MECL-1), or PSMB10] substitutes the β2 subunit,

iβ5 [LMP7 or PSMB8] substitutes the β5 subunit,

PA28α and PA28β (Proteasome Activators) replace the 19S regulatory caps.

The subunits upon signaling by inflammatory cytokines, assemble to create the immunoproteasome. Also, inhibition of the immunoproteasome leads to reduced cytokines as well.