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Updated: Aug 9, 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

CUTL1 is phosphorylated by protein kinase A, modulating its effects on cell proliferation and motility

Patrick Michl1, Beate Knobel, Julian Downward

  • 1Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.

The Journal of Biological Chemistry
|April 1, 2006
PubMed

Insights

Protein kinase A (PKA) directly phosphorylates the CUTL1 transcription factor, reducing its DNA binding and inhibiting cell cycle progression and motility. This discovery reveals a new mechanism by which PKA modulates tumor cell behavior.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • CUTL1 (CCAAT Displacement Protein 1) is a homeodomain transcription factor crucial for development and cell cycle control.
  • Previous research identified CUTL1 as a regulator of cell motility and invasiveness.
  • Protein kinase A (PKA) is recognized for its tumor-suppressive roles in various cancer types.

Purpose of the Study:

  • To investigate the direct interaction between PKA and CUTL1.
  • To elucidate the functional consequences of PKA-mediated CUTL1 phosphorylation.
  • To determine PKA's role in regulating CUTL1's impact on tumor progression.

Main Methods:

  • Phosphorylation site mapping using NIH3T3 fibroblasts.
  • Assessment of CUTL1 DNA binding affinity post-phosphorylation.
  • Analysis of CUTL1-mediated cell cycle progression and motility.
  • Quantitative analysis of CUTL1 target gene expression (e.g., DNA polymerase A, DKK2).

Main Results:

  • PKA directly phosphorylates CUTL1 at serine 1215.
  • This phosphorylation decreases CUTL1's DNA binding affinity.
  • PKA-induced CUTL1 phosphorylation impairs cell cycle progression and cell motility.
  • Expression of CUTL1 target genes involved in proliferation and migration is modulated by PKA.

Conclusions:

  • CUTL1 is a novel direct target of PKA.
  • PKA-mediated phosphorylation of CUTL1 inhibits its function.
  • This pathway represents a new mechanism for PKA to control tumor cell motility and progression.

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