Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future Directions
Thimet oligopeptidase (EC 3.4.24.15; EP24.15, THOP1) is a metallopeptidase ubiquitously distributed in mammalian tissues. Beyond its previously well characterized role in major histocompatibility class I (MHC-I) antigen presentation, the recent characterization of the THOP1 C57BL6/N null mice (THOP1...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/9/1229 |
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| author | Emer S. Ferro Mayara C. F. Gewehr Ami Navon |
| author_facet | Emer S. Ferro Mayara C. F. Gewehr Ami Navon |
| author_sort | Emer S. Ferro |
| collection | DOAJ |
| description | Thimet oligopeptidase (EC 3.4.24.15; EP24.15, THOP1) is a metallopeptidase ubiquitously distributed in mammalian tissues. Beyond its previously well characterized role in major histocompatibility class I (MHC-I) antigen presentation, the recent characterization of the THOP1 C57BL6/N null mice (THOP1<sup>−/−</sup>) phenotype suggests new key functions for THOP1 in hyperlipidic diet-induced obesity, insulin resistance and non-alcoholic liver steatosis. Distinctive levels of specific intracellular peptides (InPeps), genes and microRNAs were observed when comparing wild type C57BL6/N to THOP1<sup>−/−</sup> fed either standard or hyperlipidic diets. A possible novel mechanism of action was suggested for InPeps processed by THOP1, which could be modulating protein-protein interactions and microRNA processing, thus affecting the phenotype. Together, research into the biochemical and biomedical significance of THOP1 suggests that degradation by the proteasome is a step in the processing of various proteins, not merely for ending their existence. This allows many functional peptides to be generated by proteasomal degradation in order to, for example, control mRNA translation and the formation of protein complexes. |
| first_indexed | 2024-03-10T16:53:44Z |
| format | Article |
| id | doaj.art-34fb018298dc412b8e618cf73c010b01 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T16:53:44Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-34fb018298dc412b8e618cf73c010b012023-11-20T11:13:19ZengMDPI AGBiomolecules2218-273X2020-08-01109122910.3390/biom10091229Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future DirectionsEmer S. Ferro0Mayara C. F. Gewehr1Ami Navon2Pharmacology Department, Biomedical Science Institute, University of São Paulo, São Paulo, SP 05508-000, BrazilPharmacology Department, Biomedical Science Institute, University of São Paulo, São Paulo, SP 05508-000, BrazilDepartment of Biological Regulation, The Weizmann Institute of Science, Rehovot 7610001, IsraelThimet oligopeptidase (EC 3.4.24.15; EP24.15, THOP1) is a metallopeptidase ubiquitously distributed in mammalian tissues. Beyond its previously well characterized role in major histocompatibility class I (MHC-I) antigen presentation, the recent characterization of the THOP1 C57BL6/N null mice (THOP1<sup>−/−</sup>) phenotype suggests new key functions for THOP1 in hyperlipidic diet-induced obesity, insulin resistance and non-alcoholic liver steatosis. Distinctive levels of specific intracellular peptides (InPeps), genes and microRNAs were observed when comparing wild type C57BL6/N to THOP1<sup>−/−</sup> fed either standard or hyperlipidic diets. A possible novel mechanism of action was suggested for InPeps processed by THOP1, which could be modulating protein-protein interactions and microRNA processing, thus affecting the phenotype. Together, research into the biochemical and biomedical significance of THOP1 suggests that degradation by the proteasome is a step in the processing of various proteins, not merely for ending their existence. This allows many functional peptides to be generated by proteasomal degradation in order to, for example, control mRNA translation and the formation of protein complexes.https://www.mdpi.com/2218-273X/10/9/1229peptide metabolismpeptidaseproteaseproteasomeprotein-protein interactionmicroRNA |
| spellingShingle | Emer S. Ferro Mayara C. F. Gewehr Ami Navon Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future Directions Biomolecules peptide metabolism peptidase protease proteasome protein-protein interaction microRNA |
| title | Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future Directions |
| title_full | Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future Directions |
| title_fullStr | Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future Directions |
| title_full_unstemmed | Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future Directions |
| title_short | Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future Directions |
| title_sort | thimet oligopeptidase biochemical and biological significances past present and future directions |
| topic | peptide metabolism peptidase protease proteasome protein-protein interaction microRNA |
| url | https://www.mdpi.com/2218-273X/10/9/1229 |
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