Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

11.2K
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...
11.2K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

13.5K
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...
13.5K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

6.8K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
6.8K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

3.5K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.5K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

8.8K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.8K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

6.1K
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...
6.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Molecular basis of DNA recognition by the HMG-box-C1 module of capicua.

Structure (London, England : 1993)·2025
Same author

Regulation of Drosophila brain development and organ growth by the Minibrain/Rala signaling network.

G3 (Bethesda, Md.)·2024
Same author

Regulation of brain development by the Minibrain/Rala signaling network.

bioRxiv : the preprint server for biology·2024
Same author

The Drosophila tumour suppressor Lgl and Vap33 activate the Hippo pathway through a dual mechanism.

Journal of cell science·2024
Same author

Stochastic phenotypes in RAS-dependent developmental diseases.

Current biology : CB·2023
Same author

NDR kinase tricornered genetically interacts with Ccm3 and metabolic enzymes in Drosophila melanogaster tracheal development.

G3 (Bethesda, Md.)·2023
Same journal

Disentangling the response to lysosomal damage.

Journal of cell science·2026
Same journal

The force, form and function of the nucleus.

Journal of cell science·2026
Same journal

The nucleus-vacuole junction at a glance.

Journal of cell science·2026
Same journal

Loss of INPP5E affects photoreceptor outer segment membrane biogenesis in iPSC-derived human retinal organoids.

Journal of cell science·2026
Same journal

Brinker regulates reciprocal outcomes of BMP signal between stem cells and differentiating cells.

Journal of cell science·2026
Same journal

Primary cilium disassembly - from mechanisms to roles in physiology and disease.

Journal of cell science·2026
See all related articles

Related Experiment Video

Updated: Mar 6, 2026

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

7.0K

ERK inhibits Capicua repressor function via multisite phosphorylation.

Sayantanee Paul1,2, Khandan Ilkhani1, Nathan Strozewski1

  • 1Department of Biology, University of Massachusetts Boston, Boston, MA 02125, USA.

Journal of Cell Science
|March 5, 2026
PubMed
Summary
This summary is machine-generated.

Extracellular signal-regulated kinase (ERK) signaling regulates cell growth and survival. This study identifies key phosphorylation sites on the Capicua (Cic) protein, revealing how ERK controls Cic activity and degradation.

Keywords:
CapicuaDrosophilaERKMultisite phosphorylationPhosphodegron

More Related Videos

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

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

Published on: July 26, 2019

9.0K
Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

3.4K

Related Experiment Videos

Last Updated: Mar 6, 2026

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

7.0K
Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

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

Published on: July 26, 2019

9.0K
Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

3.4K

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Genetics

Background:

  • The receptor tyrosine kinase (RTK)/extracellular signal-regulated kinase (ERK) pathway is crucial for cellular functions.
  • Capicua (Cic) is a transcriptional repressor targeted by ERK; mutations in human CIC are linked to diseases.
  • Understanding Cic phosphorylation by ERK is vital for deciphering its regulatory mechanisms.

Purpose of the Study:

  • To identify and characterize specific phosphorylation sites on Drosophila Cic targeted by ERK.
  • To validate the in vivo developmental functions of these phosphosites using mutant Cic variants.
  • To elucidate the role of multisite phosphorylation in Cic downregulation and degradation.

Main Methods:

  • Phosphoproteomic analysis to identify potential ERK target sites on Cic.
  • Site-directed mutagenesis to create Cic variants with mutated phosphosites.
  • In vivo functional assays in Drosophila to assess the impact of mutations on Cic activity and degradation.

Main Results:

  • Identified multiple high-confidence Cic phosphosites directly targeted by ERK.
  • Cic mutated at 20 sites showed resistance to proteasomal degradation, acting as a "super-repressor".
  • ERK requires simultaneous phosphorylation of multiple Cic sites for full downregulation, suggesting a phosphodegron mechanism.

Conclusions:

  • Multisite phosphorylation by ERK is essential for the functional downregulation and degradation of Cic.
  • This mechanism involves phosphodegrons recognized by ubiquitin ligases like Ago/FBXW7.
  • The findings provide critical insights into signal interpretation downstream of the RTK/ERK pathway.