Related Experiment Video

Updated: Aug 23, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

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

Published on: May 3, 2018

Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21(Waf1/Cip1)

R Göke1, P Barth, A Schmidt

  • 1Clinical Research Unit, University Hospital of Marburg, Baldingerstrasse, D-35033 Marburg, Germany. rgoeke@gmx.net

American Journal of Physiology. Cell Physiology
|August 20, 2004
PubMed

Insights

The tumor suppressor pdcd4 inhibits cancer cell proliferation by repressing cyclin-dependent kinase 1 (CDK1). Loss of pdcd4 expression correlates with tumor progression, suggesting pdcd4 as a potential therapeutic target for cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Cycle Regulation

Background:

  • The tumor suppressor pdcd4 (programmed cell death 4) plays a critical role in regulating cell proliferation and apoptosis.
  • Upregulation of cyclin-dependent kinase 1 (CDK1)/cdc2 is associated with malignant transformation in various cancers, including colon cancer.
  • Understanding the regulatory mechanisms of CDK1/cdc2 is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To elucidate the mechanism by which pdcd4 represses CDK1/cdc2 transcription.
  • To investigate the correlation between pdcd4 expression and tumor progression in different types of cancer.
  • To evaluate the potential of targeting CDK1/cdc2 for antineoplastic therapies.

Main Methods:

  • Investigated the transcriptional regulation of CDK1/cdc2 by pdcd4.
  • Analyzed the expression and localization of pdcd4 in various human carcinomas (lung, breast, colon, prostate).
  • Assessed the effect of the CDK1/cdc2 inhibitor roscovitine on tumor cell proliferation.

Main Results:

  • Pdcd4 represses CDK1/cdc2 transcription via upregulation of p21(Waf1/Cip1), which inhibits CDK2/4/6, leading to enhanced pRb/E2F/DP binding and repression of the cdc2 promoter.
  • Pdcd4 expression is lost in progressed carcinomas of the lung, breast, colon, and prostate, with its localization and expression correlating directly with tumor progression.
  • The CDK1/cdc2 inhibitor roscovitine demonstrated reduced proliferation in multiple tumor cell lines.

Conclusions:

  • Pdcd4 acts as an indirect suppressor of CDK1/cdc2, and its loss is linked to cancer progression.
  • Targeting CDK1/cdc2, potentially through modulation of pdcd4, represents a promising strategy for antineoplastic therapies.
  • Pdcd4 may serve as a novel therapeutic target for treating various malignancies.

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

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

Published on: June 6, 2017

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...
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...
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.
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...
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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...