TY - JOUR
T1 - PP2A-mediated regulation of ras signaling in G2 is essential for stable quiescence and normal G1 length
AU - Naetar, Nana
AU - Soundarapandian, Velmurugan
AU - Litovchick, Larisa
AU - Goguen, Kelsey L.
AU - Sablina, Anna A.
AU - Bowman-Colin, Christian
AU - Sicinski, Piotr
AU - Hahn, William C.
AU - DeCaprio, James A.
AU - Livingston, David M.
N1 - Funding Information:
We wish to thank Dr. Charles Sherr for suggesting the G2-Ras hypothesis to us. We also thank Dr. William Kim and members of the D.M.L. laboratory for helpful discussions and Drs. Sergio Nasi, Subhashini Sadasivam, and Wojciech Michowski for providing reagents. This study was supported by grant NCI-P01CA50661 from the National Cancer Institute to D.M.L. N.N.’s work was supported in part by a Schroedinger fellowship from the Austrian Science Fund (FWF) and an APART fellowship of the Austrian Academy of Sciences.
PY - 2014/6/19
Y1 - 2014/6/19
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molcel.2014.04.023
DO - 10.1016/j.molcel.2014.04.023
M3 - Article
C2 - 24857551
AN - SCOPUS:84903576652
SN - 1097-2765
VL - 54
SP - 932
EP - 945
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -