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The Proliferation-Quiescence Decision Is Controlled by a Bifurcation in CDK2 Activity at Mitotic Exit
Open accessAbstract
SUMMARY Tissue homeostasis in metazoans is regulated by transitions of cells between quiescence and proliferation. The hallmark of proliferating populations is progression through the cell cycle, which is driven by cyclin-dependent kinase (CDK) activity. Here, we introduce a live-cell sensor for CDK2 activity and unexpectedly found that proliferating cells bifurcate into two populations as they exit mitosis. Many cells immediately commit to the next cell cycle by building up CDK2 activity from an intermediate level, while other cells lack CDK2 activity and enter a transient state of quiescence. This bifurcation is directly controlled by the CDK inhibitor p21 and is regulated by mitogens during a restriction window at the end of the previous cell cycle. Thus, cells decide at the end of mitosis to either start the next cell cycle by immediately building up CDK2 activity or to enter a transient G0-like state by suppressing CDK2 activity.
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Cites
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What's taking so long? S-phase entry from quiescence versus proliferation
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Treating cancer with selective CDK4/6 inhibitors
O'Leary, B., Finn, R. S., & Turner, N. C. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.26 · Cited by 1,137
Forging a signature of in vivo senescence
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Wutz, G., Várnai, C., Nagasaka, K., Cisneros, D. A., Stocsits, R. R., Tang, W., Schoenfelder, S., Jessberger, G., Muhar, M., Hossain, M. J., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201798004 · Cited by 864
The control of DNA repair by the cell cycle
Hustedt, N., & Durocher, D. (2017) · Nature Cell Biology · doi:10.1038/ncb3452 · Cited by 738
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Metadata
- Authors
- Spencer, S. L., Cappell, S. D., Tsai, F.-C., Overton, K. W., Wang, C. L., & Meyer, T.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 155
- Issue
- 2
- Pages
- 369-383
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2065782380
- Cited by
- 698
- References
- 6
- FWCI
- 15.65
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Spencer, S. L., Cappell, S. D., Tsai, F.-C., Overton, K. W., Wang, C. L., & Meyer, T. (2013). The Proliferation-Quiescence Decision Is Controlled by a Bifurcation in CDK2 Activity at Mitotic Exit. Cell. https://doi.org/10.1016/j.cell.2013.08.062
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