You are here

Mol Cell DOI:10.1016/j.molcel.2014.04.023

PP2A-mediated regulation of Ras signaling in G2 is essential for stable quiescence and normal G1 length.

Publication TypeJournal Article
Year of Publication2014
AuthorsNaetar, N, Soundarapandian, V, Litovchick, L, Goguen, KL, Sablina, AA, Bowman-Colin, C, Sicinski, P, Hahn, WC, DeCaprio, JA, Livingston, DM
JournalMol Cell
Date Published2014 Jun 19
KeywordsCell Line, Cyclin E, G1 Phase, G2 Phase, Humans, MCF-7 Cells, Mitosis, Oncogene Protein p21(ras), Protein Phosphatase 2, Protein Subunits, Resting Phase, Cell Cycle, RNA Interference, RNA, Small Interfering, Signal Transduction

Quiescence (G0) allows cycling cells to reversibly cease proliferation. A decision to enter quiescence is suspected of occurring early in G1, before the restriction point (R). Surprisingly, we have identified G2 as an interval during which inhibition of the protein phosphatase PP2A results in failure to exhibit stable quiescence. This effect is accompanied by shortening of the ensuing G1. The PP2A subcomplex required for stable G0 contains the B56γ B subunit. After PP2A inhibition in G2, aberrant overexpression of cyclin E occurs during mitosis and is responsible for overriding quiescence. Strikingly, suppression of Ras signaling re-establishes normal cyclin E levels during M and restores G0. These data point to PP2A-B56γ-driven Ras signaling modulation in G2 as essential for suppressing aberrant cyclin E expression during mitosis and thereby achieving normal G0 control. Thus, G2 is an interval during which the length and growth factor dependence of the next G1 interval are established.


Alternate JournalMol. Cell
PubMed ID24857551
PubMed Central IDPMC4118046
Grant ListP01 CA050661 / CA / NCI NIH HHS / United States
P01CA50661 / CA / NCI NIH HHS / United States