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Related Concept Videos

Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
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...
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Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Receptor Downregulation in MVBs

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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...
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Protein Translocation Machinery on the ER Membrane

The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
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Updated: May 8, 2026

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

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Published on: May 10, 2022

The TREX1 C-terminal region controls cellular localization through ubiquitination.

Clinton D Orebaugh1, Jason M Fye, Scott Harvey

  • 1From the Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157.

The Journal of Biological Chemistry
|August 28, 2013
PubMed
Summary

TREX1 ubiquitination, controlled by its C-terminal region, affects cellular localization. Dysfunctional TREX1 mutants in autoimmune diseases show altered ubiquitination and localization, revealing a novel disease mechanism.

Keywords:
Autoimmune DiseasesDNADNA EnzymesNucleic AcidUbiquitination

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Last Updated: May 8, 2026

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09:02

Mass Spectrometry Analysis to Identify Ubiquitylation of EYFP-tagged CENP-A (EYFP-CENP-A)

Published on: June 10, 2020

Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • TREX1 is a 3'-exonuclease that degrades DNA, preventing aberrant immune responses.
  • Its C-terminal region (CTR) is crucial for cytosolic localization.
  • Dysregulation of TREX1 is implicated in autoimmune diseases like Aicardi-Goutières syndrome and lupus erythematosus.

Purpose of the Study:

  • To investigate the role of TREX1 ubiquitination in its cellular localization and function.
  • To identify proteins interacting with the TREX1 CTR.
  • To explore how disease-associated TREX1 mutations affect ubiquitination and localization.

Main Methods:

  • Transfection of TREX1 deletion constructs in human cells.
  • Proteomic analysis to identify interacting proteins.
  • In vitro and in vivo interaction verification.
  • Co-transfection studies to assess TREX1 localization.
  • Analysis of TREX1 mutants linked to autoimmune diseases.

Main Results:

  • A conserved sequence in the TREX1 CTR controls ubiquitination at multiple lysine residues via a non-canonical linkage.
  • Ubiquilin 1 was identified as a TREX1 CTR-interacting protein.
  • Ubiquilin 1 mediates TREX1 localization to cytosolic puncta, dependent on the CTR and catalytic core lysines.
  • Catalytically active TREX1 mutants associated with autoimmune diseases exhibit altered ubiquitination and ubiquilin 1 co-localization.

Conclusions:

  • TREX1 post-translational modification by ubiquitination is a key regulator of its cellular localization.
  • Ubiquilin 1 plays a significant role in TREX1 trafficking.
  • Altered ubiquitination of disease-associated TREX1 mutants represents a novel mechanism contributing to autoimmune pathogenesis.
  • This highlights post-translational modification as a critical factor in TREX1-related autoimmune diseases.