The Molecular Mechanisms Governing the Assembly of the Immuno- and Thymoproteasomes in the Presence of Constitutive Proteasomes

The proteasome is a large protein complex responsible for proteolysis in cells. Though the proteasome is widely conserved in all eukaryotes, vertebrates additionally possess tissue-specific proteasomes, termed immunoproteasomes and thymoproteasomes. These specialized proteasomes diverge from constitutive proteasomes in the makeup of their catalytic 20S core particle (CP), whereby the constitutive beta 1, beta 2, and beta 5 catalytic subunits are replaced by beta 1i, beta 2i, and beta 5i in immunoproteasomes, or beta 1i, beta 2i, and beta 5t in thymoproteasomes. However, as constitutive beta 1, beta 2, and beta 5 are also present in tissues and cells expressing immuno- and thymoproteasomes, the specialized proteasomes must be able to selectively incorporate their specific subunits. Here, we review the mechanisms governing the assembly of constitutive and specialized proteasomes elucidated thus far. Studies have revealed that beta 1i and beta 2i are added onto the alpha-ring of the CP prior to the other beta subunits. Furthermore, beta 5i and beta 5t can be incorporated independent of beta 4, whereas constitutive beta 5 incorporation is dependent on beta 4. These mechanisms allow the immuno- and thymoproteasomes to integrate tissue-specific beta-subunits without contamination from constitutive beta 1, beta 2, and beta 5. We end the review with a brief discussion on the diseases caused by mutations to the immunoproteasome and the proteins involved with its assembly.