Related Experiment Video

Updated: May 5, 2026

Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
10:52

Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation

Published on: January 6, 2016

9.8K

IP-1: a dominant inhibitor of Fos/Jun whose activity is modulated by phosphorylation

J Auwerx1, P Sassone-Corsi

  • 1Laboratoire de Génétique Moléculaire, Eucaryotes du CNRS, Faculté de Médecine, Strasbourg, France.

Cell
|March 8, 1991
PubMed

Insights

A novel inhibitory protein (IP-1) blocks the activity of transcription factor AP-1 by preventing DNA binding. Phosphorylation by PKA inactivates IP-1, suggesting a cross-talk mechanism that may regulate gene transcription.

Area of Science:

  • Molecular Biology
  • Cell Signaling

Background:

  • Transcription factor AP-1, a dimer of Fos and Jun proteins, binds TPA-responsive elements (TREs) and is a key target in protein kinase C signaling.
  • AP-1 activity is crucial for regulating gene expression in response to various stimuli.

Purpose of the Study:

  • To identify and characterize novel regulators of AP-1 DNA-binding activity.
  • To investigate the mechanism by which AP-1 activity is modulated in different cellular compartments.

Main Methods:

  • Nuclear and cytoplasmic extracts from various cell types were analyzed for AP-1 modulators.
  • In vitro assays using synthesized Fos/Jun proteins and nuclear extracts were performed.
  • Phosphorylation studies involving Protein Kinase A (PKA) and competition assays with synthetic peptides were conducted.

Main Results:

  • An inhibitory protein (IP-1) of 30-40 kDa was identified, present in both nuclear and cytoplasmic fractions.
  • IP-1 specifically inhibits the DNA-binding activity of AP-1 from nuclear extracts and in vitro synthesized Fos/Jun proteins.
  • IP-1's inhibitory function requires its nonphosphorylated state; PKA-mediated phosphorylation blocks its activity, indicating potential cross-talk.
  • Competition experiments suggest IP-1 interacts with the leucine zipper regions of Fos and/or Jun.

Conclusions:

  • IP-1 acts as a negative regulator of AP-1 DNA binding, modulating its transcriptional activity.
  • PKA-mediated phosphorylation of IP-1 offers a potential mechanism for regulating AP-1 dependent transcription.
  • IP-1 may function as a transcriptional antioncogene, playing a role in controlling cell proliferation and differentiation.

More Related Videos

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

7.9K
Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases06:56

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases

Published on: September 6, 2024

856

Related Concept Videos

Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
44.1K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.1K
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...
7.7K
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...
15.3K
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...
10.2K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K