Transcription factor RFX1 is ubiquitinated by E3 ligase STUB1 in systemic lupus erythematosus

•RFX1 is degraded by ubiquitin-proteasome system in CD4+ T cells.•STUB1 mediates the degradation of RFX1 via ubiquitination.•STUB1 is upregulated in SLE CD4+ T cells.•Ubiquitination of RFX1 is increased in SLE CD4+ T cells.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease caused by complex interactions between genes and the environment. The expression level of transcription factor regulatory factor X 1 (RFX1) is reduced in T cells from SLE patients. RFX1 can regulate epigenetic modifications of CD70 and CD11a and plays an important role in the development of SLE. However, the mechanisms that mediate reduction of RFX1 in SLE are unclear. Here, we demonstrate that RFX1 protein expression can be tightly regulated by polyubiquitination-mediated proteosomal degradation via STIP1 homology and U-box containing protein 1 (STUB1). The E3 ligase STUB1 is upregulated in CD4+ T cells of SLE patients compared to healthy subjects. Overexpression of STUB1 in CD4+ T cells leads to upregulation of levels of CD70 and CD11a in T cells. The modulation of STUB1 activity may provide a novel therapeutic approach for SLE.