title: Evolution of proteasome regulators in eukaryotes.
abstract: All living organisms require protein degradation to terminate biological processes and remove damaged proteins. One such machine is the 20S proteasome, a specialized barrel-shaped and compartmentalized multicatalytic protease. The activity of the 20S proteasome generally requires the binding of regulators/proteasome activators (PAs), which control the entrance of substrates. These include the PA700 (19S complex), which assembles with the 20S and forms the 26S proteasome and allows the efficient degradation of proteins usually labeled by ubiquitin tags, PA200 and PA28, which are involved in proteolysis through ubiquitin-independent mechanisms and PI31, which was initially identified as a 20S inhibitor in vitro. Unlike 20S proteasome, shown to be present in all Eukaryotes and Archaea, the evolutionary history of PAs remained fragmentary. Here, we made a comprehensive survey and phylogenetic analyses of the four types of regulators in 17 clades covering most of the eukaryotic supergroups. We found remarkable conservation of each PA700 subunit in all eukaryotes, indicating that the current complex PA700 structure was already set up in the last eukaryotic common ancestor (LECA). Also present in LECA, PA200, PA28, and PI31 showed a more contrasted evolutionary picture, because many lineages have subsequently lost one or two of them. The paramount conservation of PA700 composition in all eukaryotes and the dynamic evolution of PA200, PA28, and PI31 are discussed in the light of current knowledge on their physiological roles.
authors.affiliation: CNRS, CRBM, UMR5237, Montpellier, France Université de Montpellier, France philippe.fort@crbm.cnrs.fr olivier.coux@crbm.cnrs.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fort
authors.affiliation: CNRS, CRBM, UMR5237, Montpellier, France Université de Montpellier, France Institut de Biologie Computationnelle, Montpellier, France.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kajava
authors.affiliation: Université de Montpellier, France CNRS, IRD, Institut des Sciences de l'Evolution, UMR 5554, Montpellier, France.
authors.forename: Fredéric
authors.initials: F
authors.lastname: Delsuc
authors.affiliation: CNRS, CRBM, UMR5237, Montpellier, France Université de Montpellier, France philippe.fort@crbm.cnrs.fr olivier.coux@crbm.cnrs.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Coux
mesh_terms: D000818:Animals; D001105:Archaea / Q000235:genetics; D056890:Eukaryota / Q000145:classification / Q000235:genetics; D019143:Evolution, Molecular; D017353:Gene Deletion; D020440:Gene Duplication; D023281:Genomics; D010802:Phylogeny; D046988:Proteasome Endopeptidase Complex / Q000145:classification / Q000235:genetics*
chemical_list: C085834:PA700 proteasome activator; D046988:Proteasome Endopeptidase Complex
keywords: PA200; PA28; PA700; PI31; evolution; proteasome