Related Experiment Video
Updated: Mar 27, 2026
09:45
In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity
Published on: January 29, 2018
9.8K
Endogenous TRIM5α Function Is Regulated by SUMOylation and Nuclear Sequestration for Efficient Innate Sensing in
Débora M Portilho1, Juliette Fernandez1, Mathieu Ringeard2
1INSERM U941, University Institute of Hematology, Saint-Louis Hospital, 75010 Paris, France.
Cell Reports
|January 11, 2016
Summary
Dendritic cells (DCs) minimize retroviral restriction by TRIM5α to enhance immune sensing. This nuclear sequestration of TRIM5α allows potent type I interferon responses, suggesting an evolutionary trade-off in immune cells.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Retroviral infection is controlled by cellular restriction factors like TRIM5α.
- Dendritic cells (DCs) play a crucial role in initiating immune responses against pathogens.
Purpose of the Study:
- To investigate the role of TRIM5α in retroviral restriction within dendritic cells.
- To understand the mechanism regulating TRIM5α activity and its impact on immune responses.
Main Methods:
- Analysis of TRIM5α localization and function in human and non-human primate DCs.
- SUMOylation assays and use of SUMOylation inhibitors (ginkgolic acid).
- Assessment of type I interferon (IFN) production and viral restriction upon manipulation of TRIM5α.
Main Results:
- Dendritic cells exhibit inefficient TRIM5α-mediated retroviral restriction.
- Endogenous TRIM5α accumulates in nuclear bodies in a SUMOylation-dependent manner in DCs.
- Nuclear sequestration of TRIM5α enhances type I IFN responses via cGAS sensing, while cytoplasmic TRIM5α restores restriction but impairs IFN production.
Conclusions:
- An evolutionary trade-off exists in DCs, balancing viral restriction with immune sensing.
- SUMOylation-dependent nuclear sequestration of TRIM5α is a key regulatory mechanism in DCs.
- This regulation optimizes innate immune responses to retroviral infections.
Related Concept Videos
01:45Regulation of Nuclear Protein Sorting
3.4K
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...
3.4K
01:45Tail-anchoring of Proteins in the ER Membrane
4.0K
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...
4.0K
01:16TGF - β Signaling Pathway
10.9K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.9K
01:15Receptor Downregulation in MVBs
3.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
3.0K
02:58Regulated Protein Degradation
9.2K
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...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
9.2K
01:39Mitochondrial Precursor Proteins
3.9K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
3.9K