Domains in Action: Understanding Ddi1’s Diverse Functions in the Ubiquitin-Proteasome System
The ubiquitin-proteasome system (UPS) is a pivotal cellular mechanism responsible for the selective degradation of proteins, playing an essential role in proteostasis, protein quality control, and regulating various cellular processes, with ubiquitin marking proteins for degradation through a comple...
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MDPI AG
2024-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/4080 |
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| author | Artur Fabijan Bartosz Polis Agnieszka Zawadzka-Fabijan Izabela Korabiewska Krzysztof Zakrzewski Emilia Nowosławska Michał Chojnacki |
| author_facet | Artur Fabijan Bartosz Polis Agnieszka Zawadzka-Fabijan Izabela Korabiewska Krzysztof Zakrzewski Emilia Nowosławska Michał Chojnacki |
| author_sort | Artur Fabijan |
| collection | DOAJ |
| description | The ubiquitin-proteasome system (UPS) is a pivotal cellular mechanism responsible for the selective degradation of proteins, playing an essential role in proteostasis, protein quality control, and regulating various cellular processes, with ubiquitin marking proteins for degradation through a complex, multi-stage process. The shuttle proteins family is a very unique group of proteins that plays an important role in the ubiquitin-proteasome system. Ddi1, Dsk2, and Rad23 are shuttle factors that bind ubiquitinated substrates and deliver them to the 26S proteasome. Besides mediating the delivery of ubiquitinated proteins, they are also involved in many other biological processes. Ddi1, the least-studied shuttle protein, exhibits unique physicochemical properties that allow it to play non-canonical functions in the cells. It regulates cell cycle progression and response to proteasome inhibition and defines MAT type of yeast cells. The Ddi1 contains UBL and UBA domains, which are crucial for binding to proteasome receptors and ubiquitin respectively, but also an additional domain called RVP. Additionally, much evidence has been provided to question whether Ddi1 is a classical shuttle protein. For many years, the true nature of this protein remained unclear. Here, we highlight the recent discoveries, which shed new light on the structure and biological functions of the Ddi1 protein. |
| first_indexed | 2024-04-24T10:42:20Z |
| format | Article |
| id | doaj.art-6ef2533215fd47c0b5bc035a55c343d8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:42:20Z |
| publishDate | 2024-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6ef2533215fd47c0b5bc035a55c343d82024-04-12T13:20:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-04-01257408010.3390/ijms25074080Domains in Action: Understanding Ddi1’s Diverse Functions in the Ubiquitin-Proteasome SystemArtur Fabijan0Bartosz Polis1Agnieszka Zawadzka-Fabijan2Izabela Korabiewska3Krzysztof Zakrzewski4Emilia Nowosławska5Michał Chojnacki6Department of Neurosurgery, Polish-Mother’s Memorial Hospital Research Institute, 93-338 Lodz, PolandDepartment of Neurosurgery, Polish-Mother’s Memorial Hospital Research Institute, 93-338 Lodz, PolandDepartment of Rehabilitation Medicine, Faculty of Health Sciences, Medical University of Lodz, 90-419 Lodz, PolandDepartment of Rehabilitation, Faculty of Dental Medicine, Medical University of Warsaw, 02-091 Warsaw, PolandDepartment of Neurosurgery, Polish-Mother’s Memorial Hospital Research Institute, 93-338 Lodz, PolandDepartment of Neurosurgery, Polish-Mother’s Memorial Hospital Research Institute, 93-338 Lodz, PolandDepartment of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, PolandThe ubiquitin-proteasome system (UPS) is a pivotal cellular mechanism responsible for the selective degradation of proteins, playing an essential role in proteostasis, protein quality control, and regulating various cellular processes, with ubiquitin marking proteins for degradation through a complex, multi-stage process. The shuttle proteins family is a very unique group of proteins that plays an important role in the ubiquitin-proteasome system. Ddi1, Dsk2, and Rad23 are shuttle factors that bind ubiquitinated substrates and deliver them to the 26S proteasome. Besides mediating the delivery of ubiquitinated proteins, they are also involved in many other biological processes. Ddi1, the least-studied shuttle protein, exhibits unique physicochemical properties that allow it to play non-canonical functions in the cells. It regulates cell cycle progression and response to proteasome inhibition and defines MAT type of yeast cells. The Ddi1 contains UBL and UBA domains, which are crucial for binding to proteasome receptors and ubiquitin respectively, but also an additional domain called RVP. Additionally, much evidence has been provided to question whether Ddi1 is a classical shuttle protein. For many years, the true nature of this protein remained unclear. Here, we highlight the recent discoveries, which shed new light on the structure and biological functions of the Ddi1 protein.https://www.mdpi.com/1422-0067/25/7/4080ubiquitin (Ub)DNA-damage inducible protein 1 (Ddi1)ubiquitin-proteasome system (UPS)ubiquitin-like domain (UBL)ubiquitin associated domain (UBA)retroviral-like protease domain (RVP) |
| spellingShingle | Artur Fabijan Bartosz Polis Agnieszka Zawadzka-Fabijan Izabela Korabiewska Krzysztof Zakrzewski Emilia Nowosławska Michał Chojnacki Domains in Action: Understanding Ddi1’s Diverse Functions in the Ubiquitin-Proteasome System International Journal of Molecular Sciences ubiquitin (Ub) DNA-damage inducible protein 1 (Ddi1) ubiquitin-proteasome system (UPS) ubiquitin-like domain (UBL) ubiquitin associated domain (UBA) retroviral-like protease domain (RVP) |
| title | Domains in Action: Understanding Ddi1’s Diverse Functions in the Ubiquitin-Proteasome System |
| title_full | Domains in Action: Understanding Ddi1’s Diverse Functions in the Ubiquitin-Proteasome System |
| title_fullStr | Domains in Action: Understanding Ddi1’s Diverse Functions in the Ubiquitin-Proteasome System |
| title_full_unstemmed | Domains in Action: Understanding Ddi1’s Diverse Functions in the Ubiquitin-Proteasome System |
| title_short | Domains in Action: Understanding Ddi1’s Diverse Functions in the Ubiquitin-Proteasome System |
| title_sort | domains in action understanding ddi1 s diverse functions in the ubiquitin proteasome system |
| topic | ubiquitin (Ub) DNA-damage inducible protein 1 (Ddi1) ubiquitin-proteasome system (UPS) ubiquitin-like domain (UBL) ubiquitin associated domain (UBA) retroviral-like protease domain (RVP) |
| url | https://www.mdpi.com/1422-0067/25/7/4080 |
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