How the proteasome is degraded
| Autor: | Ivan Dikic, Daniela Hoeller |
|---|---|
| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Multidisciplinary Chymotrypsin biology Chemistry Trypsin Cell biology Amino acid Deubiquitinating enzyme 03 medical and health sciences 030104 developmental biology Ubiquitin Proteasome Commentaries medicine biology.protein Protein biosynthesis Signal transduction medicine.drug |
| Popis: | The proteasome is one of the major degradation machineries in eukaryotic cells. It terminates the existence of thousands of short-lived, damaged, misfolded or otherwise obsolete proteins and plays pivotal roles in protein quality control and other vital processes in the cell. However, very little has been known about the mechanisms that control and execute the destruction of the proteasome itself. In their recent report in PNAS, Cohen-Kaplan et al. (1) put into place a significant piece of this puzzle by revealing events governing the removal of proteasomes upon amino acid starvation. The 26S proteasome is a complex proteolytic machine of around 2.5 MDa. It consists of a barrel-shaped protein complex (core particle, CP) that can carry a regulatory lid (the regulatory particle, RP) on one or both ends. To be degraded in the proteasome proteins have to be tagged with Ubiquitin (Ub), in particular with chains of Ub molecules linked through lysine 48 (K48) of Ub (2). Ubiquitinated substrates are recognized by Rpn1, Rpn10, and Rpn13, three subunits of the RP that possess Ub-binding domains (3). Alternatively, substrates are delivered by Ub-binding shuttling proteins (p62, Rad23/HR23, Dsk2/PLIC/Ubiquilin, and Ddi1) that dock at the proteasome via interaction of their Ub-like domain with Rpn1, Rpn10, or Rpn13 (2). After capturing the substrate, the Ub tag is released by an RP-associated deubiquitinating enzyme whereas the substrate is unfolded and threaded through a narrow gate into the interior of the CP, where it is degraded by chymotrypsin-, trypsin-, and caspase-like proteolytic activities (2). This highly controlled process not only eliminates unwanted proteins, terminates or activates signaling pathways, and participates in cell cycle regulation but also provides an important source of amino acids for de novo protein synthesis. Correspondingly, a decline in proteasomal activity is associated with aging, cancer, neurodegenerative diseases, and other late-onset diseases. … [↵][1]1To whom correspondence should be addressed. Email: Ivan.Dikic{at}biochem2.de. [1]: #xref-corresp-1-1 |
| Databáze: | OpenAIRE |
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