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A20 regulates canonical wnt-signaling through an interaction with RIPK4
- Source :
- PloS one, vol 13, iss 5, PLoS ONE, PLoS ONE, Vol 13, Iss 5, p e0195893 (2018)
- Publication Year :
- 2018
- Publisher :
- eScholarship, University of California, 2018.
-
Abstract
- A20 is a ubiquitin-editing enzyme that is known to regulate inflammatory signaling and cell death. However, A20 mutations are also frequently found in multiple malignancies suggesting a potential role as a tumor suppressor as well. We recently described a novel role for A20 in regulating the wnt-beta-catenin signaling pathway and suppressing colonic tumor development in mice. The underlying mechanisms for this phenomenon are unclear. To study this, we first generated A20 knockout cell lines by genome-editing techniques. Using these cells, we show that loss of A20 causes dysregulation of wnt-dependent gene expression by RNAseq. Mechanistically, A20 interacts with a proximal signaling component of the wnt-signaling pathway, receptor interacting protein kinase 4 (RIPK4), and regulation of wnt-signaling by A20 occurs through RIPK4. Finally, similar to the mechanism by which A20 regulates other members of the receptor interacting protein kinase family, A20 modifies ubiquitin chains on RIPK4 suggesting a possible molecular mechanism for A20's control over the wnt-signaling pathway.
- Subjects :
- 0301 basic medicine
Small interfering RNA
lcsh:Medicine
Biochemistry
Gene Knockout Techniques
Ubiquitin
Cell Signaling
immune system diseases
hemic and lymphatic diseases
2.1 Biological and endogenous factors
Small interfering RNAs
Post-Translational Modification
Aetiology
lcsh:Science
Enzyme Chemistry
Wnt Signaling Pathway
Cancer
Regulation of gene expression
Multidisciplinary
biology
Protein Kinase Signaling Cascade
Chemistry
Kinase
Wnt signaling pathway
Protein-Serine-Threonine Kinases
Signaling Cascades
3. Good health
Cell biology
Enzymes
Precipitation Techniques
Nucleic acids
Cell lines
Signal transduction
Oxidoreductases
Biological cultures
Luciferase
Research Article
Signal Transduction
Protein Binding
General Science & Technology
Protein Serine-Threonine Kinases
Research and Analysis Methods
Enzyme Regulation
03 medical and health sciences
Genetics
Immunoprecipitation
Humans
Non-coding RNA
Tumor Necrosis Factor alpha-Induced Protein 3
Biology and life sciences
Tumor Necrosis Factor-alpha
lcsh:R
HEK 293 cells
Ubiquitination
Proteins
Cell Biology
Gene regulation
030104 developmental biology
Gene Expression Regulation
biology.protein
Enzymology
RNA
lcsh:Q
Gene expression
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- PloS one, vol 13, iss 5, PLoS ONE, PLoS ONE, Vol 13, Iss 5, p e0195893 (2018)
- Accession number :
- edsair.doi.dedup.....d5c9c3da4014de29290a3e7285c48398