UBX Domain Protein 6 Positively Regulates JAK-STAT1/2 Signaling.
Harshada KetkarAndrew G HarrisonVincent R GrazianoTingting GengLong YangAnthony T VellaPenghua WangPublished in: Journal of immunology (Baltimore, Md. : 1950) (2021)
Type I/III IFNs induce expression of hundreds of IFN-stimulated genes through the JAK/STAT pathway to combat viral infections. Although JAK/STAT signaling is seemingly straightforward, it is nevertheless subjected to complex cellular regulation. In this study, we show that an ubiquitination regulatory X (UBX) domain-containing protein, UBXN6, positively regulates JAK-STAT1/2 signaling. Overexpression of UBXN6 enhanced type I/III IFNs-induced expression of IFN-stimulated genes, whereas deletion of UBXN6 inhibited their expression. RNA viral replication was increased in human UBXN6-deficient cells, accompanied by a reduction in both type I/III IFN expression, when compared with UBXN6-sufficient cells. Mechanistically, UBXN6 interacted with tyrosine kinase 2 (TYK2) and inhibited IFN-β-induced degradation of both TYK2 and type I IFNR. These results suggest that UBXN6 maintains normal JAK-STAT1/2 signaling by stabilizing key signaling components during viral infection.
Keyphrases
- poor prognosis
- tyrosine kinase
- dendritic cells
- immune response
- induced apoptosis
- binding protein
- sars cov
- endothelial cells
- high glucose
- epidermal growth factor receptor
- genome wide
- diabetic rats
- transcription factor
- long non coding rna
- protein protein
- dna methylation
- small molecule
- signaling pathway
- cell death
- bioinformatics analysis