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Basal p21 controls population heterogeneity in cycling and quiescent cell cycle states.

Proc Natl Acad Sci U S A.. 2014-10;  111(41):E4386-93
Overton KW, Spencer SL, Noderer WL, Meyer T, Wang CL. Departments of Chemical Engineering, Stanford University, Stanford, CA 94305.
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摘要

Phenotypic heterogeneity within a population of genetically identical cells is emerging as a common theme in multiple biological systems, including human cell biology and cancer. Using live-cell imaging, flow cytometry, and kinetic modeling, we showed that two states-quiescence and cell cycling-can coexist within an isogenic population of human cells and resulted from low basal expression levels of p21, a Cyclin-dependent kinase (CDK) inhibitor (CKI). We attribute the p21-dependent heterogeneity in cell cycle activity to double-negative feedback regulation involving CDK2, p21, and E3 ubiquitin ligases. In support of this mechanism, analysis of cells at a point before cell cycle entry (i.e., before the G1/S tran... More

关键词

cell dormancy; nongenetic cell heterogeneity; positive feedback loop; synthetic uORF; tumor heterogeneity