The Proliferation-Quiescence Decision Is Controlled by a Bifurcation in CDK2 Activity at Mitotic Exit

By Sabrina L. Spencer, S. Cappell, Feng-Chiao Tsai, K. Overton, Clifford L. Wang, T. Meyer. Cell, 2013

656 citations recorded by the source corpus.

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.

Subfields: Cell Biology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/fec1d9bc4d790c8a193103707c70d5a45fc8e45d

Citations in the corpus

• Temporal Control of Mammalian Cortical Neurogenesis by m6A Methylation (2017, neutral): “…or RESOURCE SOURCE IDENTIFIER pCAG-GFP Matsuda and Cepko, 2004 Addgene plasmid: 11150 pPGK-H2B-mCherry-2A-DHB(aa994-1087)-GFP From Dr. Sergi Regot (Spencer et al., 2013) N/A Software and Algorithms Image J NIH https://imagej.nih.gov/ij/ Imaris Bitplane http://www.bitplane.com/imaris/imaris MATLAB…”
• Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins (2017, neutral): “G1-phase cells were identified by nuclear localization of DHB-mKate2 signals (Spencer et al, 2013).”