Transcription factor RFX1 is ubiquitinated by E3 ligase STUB1 in systemic lupus erythematosus.
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.
Department of Dermatology and Epigenetic Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Yu
Y
Guo
Department of Dermatology and Epigenetic Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Ming
M
Zhao
Department of Dermatology and Epigenetic Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. Electronic address: qianlu5860@gmail.com.
Qianjin
Q
Lu
D000328:Adult; D040881:CD11a Antigen / Q000235:genetics / Q000378:metabolism; D053282:CD27 Ligand / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D034622:RNA Interference; D000071716:Regulatory Factor X1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D040881:CD11a Antigen; D053282:CD27 Ligand; C000605537:RFX1 protein, human; D000071716:Regulatory Factor X1; D025801:Ubiquitin; C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
STIP1 homology and U-box containing protein 1 (STUB1); Systemic lupus erythematosus (SLE); Transcription factor regulatory factor X 1 (RFX1); Ubiquitination