PA28γ: New Insights on an Ancient Proteasome Activator
PA28 (also known as 11S, REG or PSME) is a family of proteasome regulators whose members are widely present in many of the eukaryotic supergroups. In jawed vertebrates they are represented by three paralogs, PA28α, PA28β, and PA28γ, which assemble as heptameric hetero (PA28αβ) or homo (PA28γ) rings...
| Autor principal: | |
|---|---|
| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
MDPI AG
2021-02-01
|
| Colecção: | Biomolecules |
| Assuntos: | |
| Acesso em linha: | https://www.mdpi.com/2218-273X/11/2/228 |
| _version_ | 1827602831416229888 |
|---|---|
| author | Paolo Cascio |
| author_facet | Paolo Cascio |
| author_sort | Paolo Cascio |
| collection | DOAJ |
| description | PA28 (also known as 11S, REG or PSME) is a family of proteasome regulators whose members are widely present in many of the eukaryotic supergroups. In jawed vertebrates they are represented by three paralogs, PA28α, PA28β, and PA28γ, which assemble as heptameric hetero (PA28αβ) or homo (PA28γ) rings on one or both extremities of the 20S proteasome cylindrical structure. While they share high sequence and structural similarities, the three isoforms significantly differ in terms of their biochemical and biological properties. In fact, PA28α and PA28β seem to have appeared more recently and to have evolved very rapidly to perform new functions that are specifically aimed at optimizing the process of MHC class I antigen presentation. In line with this, PA28αβ favors release of peptide products by proteasomes and is particularly suited to support adaptive immune responses without, however, affecting hydrolysis rates of protein substrates. On the contrary, PA28γ seems to be a slow-evolving gene that is most similar to the common ancestor of the PA28 activators family, and very likely retains its original functions. Notably, PA28γ has a prevalent nuclear localization and is involved in the regulation of several essential cellular processes including cell growth and proliferation, apoptosis, chromatin structure and organization, and response to DNA damage. In striking contrast with the activity of PA28αβ, most of these diverse biological functions of PA28γ seem to depend on its ability to markedly enhance degradation rates of regulatory protein by 20S proteasome. The present review will focus on the molecular mechanisms and biochemical properties of PA28γ, which are likely to account for its various and complex biological functions and highlight the common features with the PA28αβ paralog. |
| first_indexed | 2024-03-09T05:27:07Z |
| format | Article |
| id | doaj.art-48270a814ef94ad3b4a575f8876be1dd |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T05:27:07Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-48270a814ef94ad3b4a575f8876be1dd2023-12-03T12:35:26ZengMDPI AGBiomolecules2218-273X2021-02-0111222810.3390/biom11020228PA28γ: New Insights on an Ancient Proteasome ActivatorPaolo Cascio0Department of Veterinary Sciences, University of Turin, Largo P. Braccini 2, 10095 Grugliasco, ItalyPA28 (also known as 11S, REG or PSME) is a family of proteasome regulators whose members are widely present in many of the eukaryotic supergroups. In jawed vertebrates they are represented by three paralogs, PA28α, PA28β, and PA28γ, which assemble as heptameric hetero (PA28αβ) or homo (PA28γ) rings on one or both extremities of the 20S proteasome cylindrical structure. While they share high sequence and structural similarities, the three isoforms significantly differ in terms of their biochemical and biological properties. In fact, PA28α and PA28β seem to have appeared more recently and to have evolved very rapidly to perform new functions that are specifically aimed at optimizing the process of MHC class I antigen presentation. In line with this, PA28αβ favors release of peptide products by proteasomes and is particularly suited to support adaptive immune responses without, however, affecting hydrolysis rates of protein substrates. On the contrary, PA28γ seems to be a slow-evolving gene that is most similar to the common ancestor of the PA28 activators family, and very likely retains its original functions. Notably, PA28γ has a prevalent nuclear localization and is involved in the regulation of several essential cellular processes including cell growth and proliferation, apoptosis, chromatin structure and organization, and response to DNA damage. In striking contrast with the activity of PA28αβ, most of these diverse biological functions of PA28γ seem to depend on its ability to markedly enhance degradation rates of regulatory protein by 20S proteasome. The present review will focus on the molecular mechanisms and biochemical properties of PA28γ, which are likely to account for its various and complex biological functions and highlight the common features with the PA28αβ paralog.https://www.mdpi.com/2218-273X/11/2/228PA28γPA28αβproteasomeproteasome activatorproteasome gateprotein degradation |
| spellingShingle | Paolo Cascio PA28γ: New Insights on an Ancient Proteasome Activator Biomolecules PA28γ PA28αβ proteasome proteasome activator proteasome gate protein degradation |
| title | PA28γ: New Insights on an Ancient Proteasome Activator |
| title_full | PA28γ: New Insights on an Ancient Proteasome Activator |
| title_fullStr | PA28γ: New Insights on an Ancient Proteasome Activator |
| title_full_unstemmed | PA28γ: New Insights on an Ancient Proteasome Activator |
| title_short | PA28γ: New Insights on an Ancient Proteasome Activator |
| title_sort | pa28γ new insights on an ancient proteasome activator |
| topic | PA28γ PA28αβ proteasome proteasome activator proteasome gate protein degradation |
| url | https://www.mdpi.com/2218-273X/11/2/228 |
| work_keys_str_mv | AT paolocascio pa28gnewinsightsonanancientproteasomeactivator |