Cyclin C: The Story of a Non-Cycling Cyclin
The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, whi...
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MDPI AG
2019-01-01
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| author | Jan Ježek Daniel G. J. Smethurst David C. Stieg Z. A. C. Kiss Sara E. Hanley Vidyaramanan Ganesan Kai-Ti Chang Katrina F. Cooper Randy Strich |
| author_facet | Jan Ježek Daniel G. J. Smethurst David C. Stieg Z. A. C. Kiss Sara E. Hanley Vidyaramanan Ganesan Kai-Ti Chang Katrina F. Cooper Randy Strich |
| author_sort | Jan Ježek |
| collection | DOAJ |
| description | The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit transcriptional coactivator complex, the Mediator, to modulate RNA polymerase II-dependent transcription. Apart from its transcriptional regulatory function, recent research has revealed a novel signaling role for cyclin C at the mitochondria. Upon oxidative stress, cyclin C leaves the nucleus and directly activates the guanosine 5’-triphosphatase (GTPase) Drp1, or Dnm1 in yeast, to induce mitochondrial fragmentation. Importantly, cyclin C-induced mitochondrial fission was found to increase sensitivity of both mammalian and yeast cells to apoptosis. Here, we review and discuss the biology of cyclin C, focusing mainly on its transcriptional and non-transcriptional roles in tumor promotion or suppression. |
| first_indexed | 2024-03-12T06:01:52Z |
| format | Article |
| id | doaj.art-83725902348f483f9e668658ddb8cff9 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-12T06:01:52Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-83725902348f483f9e668658ddb8cff92023-09-03T04:03:06ZengMDPI AGBiology2079-77372019-01-0181310.3390/biology8010003biology8010003Cyclin C: The Story of a Non-Cycling CyclinJan Ježek0Daniel G. J. Smethurst1David C. Stieg2Z. A. C. Kiss3Sara E. Hanley4Vidyaramanan Ganesan5Kai-Ti Chang6Katrina F. Cooper7Randy Strich8Department of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USADepartment of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USADepartment of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USADepartment of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USADepartment of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USADepartment of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USADepartment of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USADepartment of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USADepartment of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USAThe class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit transcriptional coactivator complex, the Mediator, to modulate RNA polymerase II-dependent transcription. Apart from its transcriptional regulatory function, recent research has revealed a novel signaling role for cyclin C at the mitochondria. Upon oxidative stress, cyclin C leaves the nucleus and directly activates the guanosine 5’-triphosphatase (GTPase) Drp1, or Dnm1 in yeast, to induce mitochondrial fragmentation. Importantly, cyclin C-induced mitochondrial fission was found to increase sensitivity of both mammalian and yeast cells to apoptosis. Here, we review and discuss the biology of cyclin C, focusing mainly on its transcriptional and non-transcriptional roles in tumor promotion or suppression.http://www.mdpi.com/2079-7737/8/1/3cyclin familytranscriptional cyclinsCdk8-dependent kinase moduleMediatorstress signalingyeasttumor suppressorcancer |
| spellingShingle | Jan Ježek Daniel G. J. Smethurst David C. Stieg Z. A. C. Kiss Sara E. Hanley Vidyaramanan Ganesan Kai-Ti Chang Katrina F. Cooper Randy Strich Cyclin C: The Story of a Non-Cycling Cyclin Biology cyclin family transcriptional cyclins Cdk8-dependent kinase module Mediator stress signaling yeast tumor suppressor cancer |
| title | Cyclin C: The Story of a Non-Cycling Cyclin |
| title_full | Cyclin C: The Story of a Non-Cycling Cyclin |
| title_fullStr | Cyclin C: The Story of a Non-Cycling Cyclin |
| title_full_unstemmed | Cyclin C: The Story of a Non-Cycling Cyclin |
| title_short | Cyclin C: The Story of a Non-Cycling Cyclin |
| title_sort | cyclin c the story of a non cycling cyclin |
| topic | cyclin family transcriptional cyclins Cdk8-dependent kinase module Mediator stress signaling yeast tumor suppressor cancer |
| url | http://www.mdpi.com/2079-7737/8/1/3 |
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