mTORC2 Assembly Is Regulated by USP9X-Mediated Deubiquitination of RICTOR.
Hill, Sandra M
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Wrobel, L., Siddiqi, F., Hill, S. M., Son, S., Karabiyik, C., Kim, H., & Rubinsztein, D. (2020). mTORC2 Assembly Is Regulated by USP9X-Mediated Deubiquitination of RICTOR.. Cell reports, 33 (13), 108564. https://doi.org/10.1016/j.celrep.2020.108564
The mechanistic target of rapamycin complex 2 (mTORC2) controls cell metabolism and survival in response to environmental inputs. Dysregulation of mTORC2 signalling has been linked to diverse human diseases, including cancer and metabolic disorders, highlighting the importance of a tightly controlled mTORC2. While mTORC2 assembly is a critical determinant of its activity, the factors regulating this event are not well understood and it is unclear whether this process is regulated by growth factors. Here, we present data from human cell lines and mice, describing a mechanism by which growth factors regulate USP9X deubiquitinase to stimulate mTORC2 assembly and activity. USP9X removes K63-linked ubiquitin from RICTOR to promote its interaction with mTOR, thereby facilitating mTORC2 signalling. As mTORC2 is central for cellular homeostasis, understanding the mechanisms regulating mTORC2 activation towards its downstream targets is vital for our understanding of physiological processes and for developing new therapeutic strategies in pathology.
External DOI: https://doi.org/10.1016/j.celrep.2020.108564
This record's URL: https://www.repository.cam.ac.uk/handle/1810/316448
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/