Journal
CELL REPORTS
Volume 20, Issue 13, Pages 3212-3222Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.08.099
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Funding
- Cancer Center Core Support Grant [P30 CA016086]
- University Cancer Research Fund
- Susan G. Komen Foundation [CCR14298820]
- Jimmy-V Foundation
- National Institutes of Health [R01GM120309]
- NIH
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The oncogenic AKT kinase is a key regulator of apoptosis, cell growth, and cell-cycle progression. Despite its important role in proliferation, it remains largely unknown how AKT is mechanistically linked to the cell cycle. We show here that cyclin F, a substrate receptor F-box protein for the SCF (Skp1/Cul1/F-box) family of E3 ubiquitin ligases, is a bona fide AKT substrate. Cyclin F expression oscillates throughout the cell cycle, a rare feature among the 69 human F-box proteins, and all of its known substrates are involved in proliferation. AKT phosphorylation of cyclin F enhances its stability and promotes assembly into productive E3 ligase complexes. Importantly, expression of mutant versions of cyclin F that cannot be phosphorylated by AKT impair cell-cycle entry. Our data suggest that cyclin F transmits mitogen signaling through AKT to the core cell-cycle machinery. This discovery has potential implications for proliferative control in malignancies where AKT is activated.
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