Related Experiment Video

Updated: Apr 12, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

28.8K

FOXO target gene CTDSP2 regulates cell cycle progression through Ras and p21(Cip1/Waf1)

David E A Kloet1, Paulien E Polderman1, Astrid Eijkelenboom1

  • 1University Medical Centre Utrecht, Universiteitsweg 100 STR3.217, 3584CG Utrecht, The Netherlands.

The Biochemical Journal
|May 21, 2015
PubMed

Insights

FOXO transcription factors regulate cell cycle progression. New research identifies CTDSP2 as a FOXO target gene that induces cell cycle arrest by upregulating p21(Cip1/Waf1) via Ras activation.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Cancer Research

Background:

  • FOXO (forkhead box O) transcription factors regulate cellular processes, including cell cycle progression, and their activity is inhibited by growth factor-PI3K-PKB/Akt signaling.
  • Identifying genes regulated by both FOXO and PI3K-PKB/Akt signaling provides insight into cellular control mechanisms.

Purpose of the Study:

  • To identify and validate novel FOXO target genes involved in cell cycle regulation.
  • To elucidate the mechanism by which CTDSP2 influences cell cycle progression and its relationship with known signaling pathways.

Main Methods:

  • Comparative analysis of microarray datasets to identify commonly regulated genes.
  • Validation of CTDSP2 as a FOXO target gene through experimental methods.
  • Analysis of transcriptional changes following CTDSP2 expression and assessment of its phosphatase activity.
  • Investigating the role of p21(Cip1/Waf1), Ras, p53, and MEK in CTDSP2-mediated cell cycle arrest.

Main Results:

  • CTDSP2 was identified as a genuine FOXO target gene.
  • Ectopic CTDSP2 expression induced cell cycle arrest, dependent on its phosphatase activity.
  • CTDSP2 up-regulated the CDK inhibitor p21(Cip1/Waf1), which contributed to cell cycle arrest by reducing cyclin-CDK activity.
  • CTDSP2-induced p21(Cip1/Waf1) upregulation was mediated by increased Ras activity, involving both p53-dependent and independent pathways.

Conclusions:

  • CTDSP2 acts as a FOXO-regulated gene that promotes cell cycle arrest.
  • The mechanism involves CTDSP2-mediated activation of Ras, leading to p21(Cip1/Waf1) induction.
  • These findings suggest CTDSP2 is part of a broader FOXO-regulated network that modulates growth factor signaling.
Keywords:
C-terminal domain small phosphatase 2 (CTDSP2)cell cycle progression regulationforkhead box O (FOXO)gene expression regulationgrowth factor signallingp21Cip1/Waf1

More Related Videos

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.9K
Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

19.5K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

5.7K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
39.1K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.4K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.4K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
11.0K