Related Experiment Video

Updated: Mar 22, 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

19.4K

O-GlcNAcylation Antagonizes Phosphorylation of CDH1 (CDC20 Homologue 1)

Jie Tian1, Qizhi Geng1, Yuehe Ding2

  • 1From the Beijing Key Laboratory of DNA Damage Response and College of Life Sciences, Capital Normal University, Beijing 100048, China and.

The Journal of Biological Chemistry
|April 16, 2016
PubMed

Insights

The anaphase promoting complex/cyclosome (APC/C) is regulated by Cdh1, a protein now found to be modified by O-linked N-acetylglucosamine (O-GlcNAc). This O-GlcNAc modification of Cdh1 appears to antagonize its phosphorylation, impacting cell cycle control.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The anaphase promoting complex/cyclosome (APC/C) is a crucial regulator of the eukaryotic cell cycle.
  • Cdh1 is a key co-activator of the APC/C and undergoes various post-translational modifications like phosphorylation and ubiquitination.

Purpose of the Study:

  • To identify novel post-translational modifications of Cdh1.
  • To investigate the functional role of O-linked N-acetylglucosamine (O-GlcNAc) modification on Cdh1.
  • To understand how O-GlcNAcylation impacts APC/C activity.

Main Methods:

  • Mass spectrometry was employed to identify O-GlcNAcylated peptides in Cdh1.
  • Experiments utilized cultured cells and mouse brain extracts.
  • Cell synchronization and mutation studies were performed to analyze the interplay between O-GlcNAcylation and phosphorylation.

Main Results:

  • O-linked N-acetylglucosamine (O-GlcNAc) modification was identified on Cdh1 in both cultured cells and mouse brain extracts.
  • Mass spectrometry pinpointed an O-GlcNAcylated site adjacent to a known phosphorylation site on Cdh1.
  • O-GlcNAcylation of Cdh1 was observed to potentially antagonize its phosphorylation.

Conclusions:

  • This study reveals O-GlcNAcylation as a novel modification of the APC/C co-activator Cdh1.
  • The findings suggest a regulatory mechanism where O-GlcNAcylation of Cdh1 influences its phosphorylation status.
  • O-GlcNAcylation plays a significant role in modulating APC/C activity and, consequently, cell cycle progression.
Keywords:
Cdh1O-linked N-acetylglucosamine (O-GlcNAc)O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT)anaphase promoting complex/cyclosome (APC/C)cell cyclemitosisphosphorylation

More Related Videos

Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases09:13

Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases

Published on: November 22, 2024

1.9K
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

11.9K

Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
8.2K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

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,...
9.1K
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...
6.2K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

5.6K
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...
19.1K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

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