The E3 deubiquitinase USP17 is a positive regulator of retinoic acid-related orphan nuclear receptor ?t (ROR?t) in Th17 cells.

ABSTRACT: Stable retinoic acid-related orphan nuclear receptor ?t (ROR?t) expression is pivotal for the development and function of Th17 cells. Here we demonstrate that expression of the transcription factor ROR?t can be regulated through deubiquitination, which prevents proteasome-mediated degradation. We establish that USP17 stabilizes ROR?t protein expression by reducing ROR?t polyubiquitination at its Lys-360 residue. In contrast, knockdown of endogenous USP17 in Th17 cells resulted in decreased ROR?t 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 ROR?t expression in Th17 cells can be positively regulated by USP17, thereby modulating Th17 cell functions.

SUBMITTER: Han L 

PROVIDER: S-EPMC4162160 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature