Related Experiment Video

Updated: Aug 15, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Small molecule inhibitors of dual specificity protein phosphatases

K E Pestell1, A P Ducruet, P Wipf

  • 1Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261, USA.

Oncogene
|June 28, 2001
PubMed

Insights

Deregulation of cell cycle control in cancer involves altered protein phosphorylation. Targeting dual specificity protein phosphatases, like Cdc25, offers new cancer management strategies by modulating cell cycle checkpoints.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Neoplasia is characterized by deregulated cell cycle control due to altered protein phosphorylation.
  • Dual specificity protein phosphatases (DSPs) dephosphorylate serine/threonine and tyrosine residues, regulating key signaling pathways.
  • Cdc25 phosphatases, a subclass of DSPs, are crucial for cell cycle progression and are often overexpressed in human tumors, correlating with poor prognosis.

Purpose of the Study:

  • To explore the role of dual specificity protein phosphatases in cancer.
  • To investigate the therapeutic potential of targeting DSPs for cancer management.

Main Methods:

  • Analysis of protein phosphorylation in cell cycle regulation.
  • Investigating the function of Cdc25 phosphatases in cell cycle checkpoints.
  • Exploring small molecules to inhibit DSPs or alter their subcellular localization.

Main Results:

  • Altered protein phosphorylation is a hallmark of cancer, affecting cell cycle control.
  • Cdc25 phosphatases play a critical role in G1/S and G2/M cell cycle transitions.
  • DSP activity is influenced by expression levels, subcellular distribution, and proximity to substrates.

Conclusions:

  • Targeting DSPs, particularly Cdc25 phosphatases, presents a promising avenue for cancer therapy.
  • Small molecules modulating DSP activity or localization could serve as novel anti-cancer agents.
  • Further research into DSPs can illuminate phosphorylation pathway roles and improve cancer treatment strategies.

More Related Videos

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors10:17

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors

Published on: April 29, 2022

Related Concept Videos

Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: