Related Experiment Video

Updated: Dec 8, 2025

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
10:12

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

3.3K

DELTEX2 C-terminal domain recognizes and recruits ADP-ribosylated proteins for ubiquitination

Syed Feroj Ahmed1, Lori Buetow1, Mads Gabrielsen1

  • 1Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.

Science Advances
|September 16, 2020
PubMed

Insights

The DELTEX family E3 ligase DTX2 utilizes its DTC domain to bind poly-ADP-ribose (PAR) and recruit PAR-modified proteins for ubiquitination, particularly those in DNA damage repair pathways.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cellular Signaling

Background:

  • Ubiquitination and ADP-ribosylation are crucial post-translational modifications regulating signaling pathways.
  • The DELTEX (DTX) family of E3 ubiquitin ligases possess a conserved RING domain and a C-terminal domain (DTC) of unknown function.

Purpose of the Study:

  • To investigate the interactome and ubiquitinated substrates of human DTX2.
  • To elucidate the function of the DTX DTC domain in protein ubiquitination.

Main Methods:

  • Label-free mass spectrometry to identify DTX2 interactors and substrates.
  • Structural, biochemical, and cell-based assays to characterize protein-domain interactions.

Main Results:

  • DTX2 interacts with and ubiquitinates proteins involved in DNA damage repair.
  • DTX2-catalyzed ubiquitination requires PARP1/2-mediated ADP-ribosylation and the DTC domain.
  • The DTX2 DTC domain contains an ADP-ribose-binding pocket that recruits poly-ADP-ribose (PAR)-modified proteins.

Conclusions:

  • The DTX DTC domain acts as a novel ADP-ribose-binding module.
  • This domain facilitates PAR-dependent ubiquitination, a mechanism conserved across DELTEX E3 ligases.
  • Uncovers a new layer of regulation in signaling pathways involving cross-talk between ADP-ribosylation and ubiquitination.

More Related Videos

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

2.9K
Isolation of Labile Multi-protein Complexes by in vivo Controlled Cellular Cross-Linking and Immuno-magnetic Affinity Chromatography10:50

Isolation of Labile Multi-protein Complexes by in vivo Controlled Cellular Cross-Linking and Immuno-magnetic Affinity Chromatography

Published on: March 9, 2010

17.7K

Related Concept Videos

Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.5K
Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
7.1K
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
15.8K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.8K
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.4K
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
9.8K