The proliferation-quiescence decision is controlled by a bifurcation in CDK2 activity at mitotic exit. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • September 26, 2013

Research

keywords

  • Cyclin-Dependent Kinase 2
  • Mitosis

Identity

PubMed Central ID

  • PMC4001917

Scopus Document Identifier

  • 84885614963

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2013.08.062

PubMed ID

  • 24075009

Additional Document Info

volume

  • 155

issue

  • 2