Activators of the 26S proteasome when protein degradation increases
Abstract In response to extra- and intracellular stimuli that constantly challenge and disturb the proteome, cells rapidly change their proteolytic capacity to maintain proteostasis. Failure of such efforts often becomes a major cause of diseases or is associated with exacerbation. Increase in prote...
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Nature Publishing Group
2025-01-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01385-x |
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| author | Donghoon Lee |
| author_facet | Donghoon Lee |
| author_sort | Donghoon Lee |
| collection | DOAJ |
| description | Abstract In response to extra- and intracellular stimuli that constantly challenge and disturb the proteome, cells rapidly change their proteolytic capacity to maintain proteostasis. Failure of such efforts often becomes a major cause of diseases or is associated with exacerbation. Increase in protein breakdown occurs at multiple steps in the ubiquitin-proteasome system, and the regulation of ubiquitination has been extensively studied. However, the activities of the 26S proteasome are also stimulated, especially under highly catabolic conditions such as those associated with atrophying skeletal muscle, proteotoxic stress such as heat shock and arsenite, or hormonal cues such as cAMP or cGMP agonists. Among the proteins that enhance proteasomal degradation are the PKA, PKG, UBL-UBA proteins and the Zn finger AN1-type domain (ZFAND) family proteins. ZFAND proteins are of particular interest because of their inducible expression in response to various stimuli and their abilities to control protein quality by stimulating the 26S proteasome and p97/VCP. The regulatory roles of ZFAND proteins appear to be important not only for the control of protein degradation but also for other cellular processes, such as mRNA stability and signaling pathways. This review summarizes the known functions of proteasome activators and discusses their possible roles in regulating proteostasis and other cellular processes. |
| format | Article |
| id | doaj-art-c3ee68b50717410286fd3405c266004e |
| institution | Kabale University |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-c3ee68b50717410286fd3405c266004e2025-02-09T12:14:18ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-01-01571414910.1038/s12276-024-01385-xActivators of the 26S proteasome when protein degradation increasesDonghoon Lee0Department of Cell Biology, Harvard Medical School, 240 Longwood AvenueAbstract In response to extra- and intracellular stimuli that constantly challenge and disturb the proteome, cells rapidly change their proteolytic capacity to maintain proteostasis. Failure of such efforts often becomes a major cause of diseases or is associated with exacerbation. Increase in protein breakdown occurs at multiple steps in the ubiquitin-proteasome system, and the regulation of ubiquitination has been extensively studied. However, the activities of the 26S proteasome are also stimulated, especially under highly catabolic conditions such as those associated with atrophying skeletal muscle, proteotoxic stress such as heat shock and arsenite, or hormonal cues such as cAMP or cGMP agonists. Among the proteins that enhance proteasomal degradation are the PKA, PKG, UBL-UBA proteins and the Zn finger AN1-type domain (ZFAND) family proteins. ZFAND proteins are of particular interest because of their inducible expression in response to various stimuli and their abilities to control protein quality by stimulating the 26S proteasome and p97/VCP. The regulatory roles of ZFAND proteins appear to be important not only for the control of protein degradation but also for other cellular processes, such as mRNA stability and signaling pathways. This review summarizes the known functions of proteasome activators and discusses their possible roles in regulating proteostasis and other cellular processes.https://doi.org/10.1038/s12276-024-01385-x |
| spellingShingle | Donghoon Lee Activators of the 26S proteasome when protein degradation increases Experimental and Molecular Medicine |
| title | Activators of the 26S proteasome when protein degradation increases |
| title_full | Activators of the 26S proteasome when protein degradation increases |
| title_fullStr | Activators of the 26S proteasome when protein degradation increases |
| title_full_unstemmed | Activators of the 26S proteasome when protein degradation increases |
| title_short | Activators of the 26S proteasome when protein degradation increases |
| title_sort | activators of the 26s proteasome when protein degradation increases |
| url | https://doi.org/10.1038/s12276-024-01385-x |
| work_keys_str_mv | AT donghoonlee activatorsofthe26sproteasomewhenproteindegradationincreases |