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Updated: Apr 19, 2026

Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
PP2A: more than a reset switch to activate pRB proteins during the cell cycle and in response to signaling cues
Alison Kurimchak1, Xavier Graña
1a Fels Institute for Cancer Research and Molecular Biology and Department of Biochemistry; Temple University School of Medicine ; Philadelphia , PA USA.
Abstract:
In their active hypophosphorylated state, members of the retinoblastoma family of pocket proteins negatively regulate cell cycle progression at least in part by repressing expression of E2F-dependent genes. Mitogen-dependent activation of G1 and G1/S Cyclin Dependent Kinases (CDKs) results in coordinated hyperphosphorylation and inactivation of these proteins, which no longer bind and repress E2Fs. S and G2/M CDKs maintain pocket protein hyperphosphorylated through the end of mitosis. The inactivating action of inducible CDKs is opposed by the Ser/Thr protein phosphatases PP2A and PP1. Various trimeric PP2A holoenzymes have been implicated in dephosphorylation of pocket proteins in response to specific cellular signals and stresses or as part of an equilibrium with CDKs throughout the cell cycle. PP1 has specifically been implicated in dephosphorylation of pRB in late mitosis and early G1. This review is particularly focused on the emerging role of PP2A as a major hub for integration of growth suppressor signals that require rapid inactivation of pocket proteins. Of note, activation of particular PP2A holoenzymes triggers differential activation of pocket proteins in the presence of active CDKs.
Insights
Protein phosphatases PP2A and PP1 oppose cyclin-dependent kinases (CDKs) by dephosphorylating pocket proteins, regulating cell cycle progression. PP2A is highlighted for its role in integrating growth suppressor signals.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Pocket proteins (e.g., pRB) in hypophosphorylated state inhibit cell cycle by repressing E2F-dependent genes.
- Cyclin-dependent kinases (CDKs) hyperphosphorylate and inactivate pocket proteins, releasing E2F repression.
- Protein phosphatases PP2A and PP1 counteract CDK activity by dephosphorylating pocket proteins.
Purpose of the Study:
- To review the role of protein phosphatase 2A (PP2A) in cell cycle regulation.
- To highlight PP2A's function as a signaling hub for growth suppression.
- To discuss the interplay between PP2A, PP1, CDKs, and pocket proteins.
Main Methods:
- Literature review focusing on cell cycle regulation and protein phosphatases.
- Analysis of the roles of PP2A and PP1 in pocket protein dephosphorylation.
- Integration of findings on CDK and phosphatase activities in cell cycle control.
Main Results:
- PP2A and PP1 oppose the cell cycle-promoting activity of CDKs on pocket proteins.
- Specific PP2A holoenzymes are involved in dephosphorylating pocket proteins in response to cellular signals.
- PP2A acts as a central integrator of growth suppressor pathways impacting pocket protein activity.
Conclusions:
- PP2A plays a critical role in cell cycle regulation by inactivating pocket proteins.
- Differential activation of PP2A holoenzymes leads to specific pocket protein inactivation.
- Understanding PP2A function is key to comprehending cell cycle control and growth suppression mechanisms.
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