Research Paper Volume 14, Issue 21 pp 8645—8660
The deubiquitylase USP7 is a novel cyclin F-interacting protein and regulates cyclin F protein stability
- 1 Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, 560012, India
- 2 Sri Shankara Cancer Hospital and Research Centre, Bengaluru, 560004, India
- 3 Department of Surgery, University of Utah Health, Huntsman Cancer Institute, Salt Lake City, UT 84132, USA
Received: October 13, 2022 Accepted: October 31, 2022 Published: November 5, 2022
https://doi.org/10.18632/aging.204372How to Cite
Copyright: © 2022 Sharma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Cyclin F, unlike canonical and transcriptional cyclins, does not bind or activate any cyclin-dependent kinases. Instead, it harbors an F-box motif and primarily functions as the substrate recognition subunit of the Skp1-Cul1-F-box E3 ubiquitin ligase complex, SCFCyclin F. By targeting specific proteins for ubiquitin-mediated proteasomal degradation, cyclin F plays a critical role in the regulation of centrosomal duplication, DNA replication and repair, and maintenance of genomic stability. Cyclin F abundance and activity are tightly regulated throughout the cell cycle. However, the molecular mechanisms regulating cyclin F are scantily understood. Here, we identify the deubiquitylase USP7 as a novel cyclin F-interacting protein. We observe that USP7 stabilizes cyclin F protein and that this function is independent of the deubiquitylase activity of USP7. Additionally, our data suggest that USP7 is also involved in the regulation of cyclin F mRNA. Pharmacological inhibition of the deubiquitylase activity of USP7 resulted in downregulation of cyclin F mRNA.