Origin and evolution of the specialized forms of proteasomes involved in antigen presentation
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Proteasomes are a multi-subunit protease complex that produces peptides bound by major histocompatibility complex (MHC) class I molecules. Phylogenetic studies indicate that two specialized forms of proteasomes, immunoproteasomes and thymoproteasomes, and the proteasome activator PA28αβ emerged in a common ancestor of jawed vertebrates which acquired adaptive immunity based on the MHC, T cell receptors, and B cell receptors ~ 500 million years ago. Comparative genomics studies now provide strong evidence that the genes coding for the immunoproteasome subunits emerged by genome-wide duplication. On the other hand, the gene encoding the thymoproteasome subunit β5t emerged by tandem duplication from the gene coding for the β5 subunit. Strikingly, birds lack immunoproteasomes, thymoproteasomes, and the proteasome activator PA28αβ, raising an interesting question of whether they have evolved any compensatory mechanisms.
KeywordsAdaptive immune system Genome-wide duplication Immunoproteasome Proteasome activator Thymoproteasome
We thank Dr. Yoichi Sutoh, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, for his help in preparing Fig. 2.
Experimental work from the authors’ laboratories has been supported by grants from The Ministry of Education, Culture, Sports, Science and Technology, Japan, and The National Institutes of Health, USA (RO1AI140326).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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