The E3 Deubiquitinase USP17 Is a Positive Regulator of Retinoic Acid-related Orphan Nuclear Receptor γt (RORγt) in Th17 Cells
Copyright policy )The E3 Deubiquitinase USP17 Is a Positive Regulator of Retinoic Acid-related Orphan Nuclear Receptor γt (RORγt) in Th17 Cells
Stable retinoic acid-related orphan nuclear receptor γt (RORγt) expression is pivotal for the development and function of Th17 cells. Here we demonstrate that expression of the transcription factor RORγt can be regulated through deubiquitination, which prevents proteasome-mediated degradation. We establish that USP17 stabilizes RORγt protein expression by reducing RORγt polyubiquitination at its Lys-360 residue. In contrast, knockdown of endogenous USP17 in Th17 cells resulted in decreased RORγt protein levels and down-regulation of Th17-related genes. Furthermore, USP17 expression was up-regulated in CD4(+) T cells from systemic lupus erythematosus patients. Our data reveal a molecular mechanism in which RORγt expression in Th17 cells can be positively regulated by USP17, thereby modulating Th17 cell functions.
- Chinese Academy of Sciences
- Renji Hospital China (People's Republic of)
- Fudan University China (People's Republic of)
- Chinese Academy of Sciences
- Chinese Academy of Sciences
CD4-Positive T-Lymphocytes, Proteasome Endopeptidase Complex, Interleukin-17, Cell Differentiation, Forkhead Transcription Factors, Nuclear Receptor Subfamily 1, Group F, Member 3, Gene Expression Regulation, Enzymologic, HEK293 Cells, Endopeptidases, Proteolysis, Humans, Lupus Erythematosus, Systemic, Th17 Cells
CD4-Positive T-Lymphocytes, Proteasome Endopeptidase Complex, Interleukin-17, Cell Differentiation, Forkhead Transcription Factors, Nuclear Receptor Subfamily 1, Group F, Member 3, Gene Expression Regulation, Enzymologic, HEK293 Cells, Endopeptidases, Proteolysis, Humans, Lupus Erythematosus, Systemic, Th17 Cells
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).57 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!