Document Type

Article

Version Deposited

Published Version

Publication Date

1-4-2019

Publication Title

Biology (Basel)

DOI

10.3390/biology8010003

Abstract

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.

Comments

All articles published by MDPI are made immediately available worldwide under an open access license.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Published Citation

Jezek J, Smethurst DGJ, Stieg DC, Kiss ZAC, Hanley SE, Ganesan V, Chang KT, Cooper KF, Strich R. Cyclin C: The story of a non-cycling cyclin. [Review]. Biology (Basel). 2019 Jan 4;8(1). pii: E3. doi: 10.3390/biology8010003. PMID: 30621145.

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