# A role of PP2A-Cdc55 in cell cycle

> **NIH NIH SC1** · BROOKLYN COLLEGE · 2022 · $392,500

## Abstract

Project Summary
 The cell cycle is an ordered set of cellular processes that produces two identical
daughter cells. This process involves DNA replication and chromosome segregation leading to
cell division. Cyclin dependent kinase (Cdk1) drives eukaryotic cell cycle progression and cell
proliferation. Cdk1 is a serine/threonine kinase whose activity depends on its binding partner,
cyclin. The cyclin/Cdk1 complex phosphorylates various substrates at S/TP consensus motifs to
trigger a downstream signaling cascade. The cell cycle is a unidirectional process which is
regulated by temporal degradation of the cyclins. This Cdk1-dependent phosphorylation event is
reversed by the phosphatases PP2A and Cdc14 in S. cerevisiae. PP2A is a heterotrimer with
two possible regulatory subunits in yeast: Cdc55 or Rts1, which direct the complex to distinct
targets. PP2A-Cdc55 preferentially dephosphorylates Cdk1 substrates at threonine residues in
mitosis. Here we propose that PP2A-Cdc55 positively regulates DNA replication through Cdc6
and negatively regulates mitotic spindle elongation through Pds1 in S. cerevisiae. This
mechanism ensures unidirectional cell cycle progression to maintain genome integrity. Aberrant
cell cycle control leads to chromosome instability which is a hallmark of cancer. Our long-term
goal is to understand the role of phosphatase in control of cell proliferation and tumorigenesis.
 In this proposal, two aims will test my hypothesis that PP2A-Cdc55 promotes origin
licensing to initiate DNA replication and negatively regulates spindle elongation in S.
cerevisiae.
Aim1 will define the role of PP2A-Cdc55 in origin licensing. The general strategy of Aim1 is to
study how Cdc6 and other DNA replication proteins are regulated by PP2A-Cdc55.
Aim2 will determine how PP2A-Cdc55 dependent Pds1 dephosphorylation inhibits spindle
elongation. We will test if PP2A-Cdc55 controls spindle elongation through Pds1-Esp1 and
other downstream targets.
The PP2A is frequently found to be inactivated in cancer patients making PP2A a potential
therapeutic target. In this study, we will use a single cell model organism, S. cerevisiae, to
understand the basic mechanism of how PP2A controls the cell cycle. DNA replication and
mitosis are well conserved cellular events in eukaryotes. The yeast components focused on in
this project are well conserved in humans. The results obtained from this study can be applied
to understanding how PP2A functions in higher eukaryotes.

## Key facts

- **NIH application ID:** 10378659
- **Project number:** 5SC1GM121242-06
- **Recipient organization:** BROOKLYN COLLEGE
- **Principal Investigator:** Amy E Ikui
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2017-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378659

## Citation

> US National Institutes of Health, RePORTER application 10378659, A role of PP2A-Cdc55 in cell cycle (5SC1GM121242-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10378659. Licensed CC0.

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