Activation of the Ets transcription factor Elf-1 requires phosphorylation and glycosylation: defective expression of activated Elf-1 is involved in the decreased TCR zeta chain gene expression in patients with systemic lupus erythematosus.
Elf-1, a member of the Ets transcription factor family with an estimated molecular mass of 68 kDa, is involved in the transcriptional regulation of several hematopoietic cell genes. It is shown that following O-GlcNAc glycosylation and phosphorylation by PKC theta, the cytoplasm-located, 80-kDa Elf-1 translocates to the nucleus as a 98-kDa protein. In the nucleus, Elf-1 binds to the promoter of the TCR zeta gene and promotes its transcription in Jurkat and fresh human T cells. It is also shown that in the majority of patients with systemic lupus erythematosus (SLE), who are known to express decreased levels of T cell receptor (TCR) zeta chain and mRNA, the 80-kDa Elf-1 protein does not undergo proper post-transcriptional modification, which results in low levels of the 98-kDa protein, lack of Elf-binding to the TCR zeta promoter, and decreased gene transcription. Therefore, a novel activation pathway for a member of the Ets family of transcription factors, which is defective in patients with systemic autoimmunity, has been revealed.
Tsokos
George C
GC
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. gtsokos@usuhs.mil
Nambiar
Madhusoodana P
MP
Juang
Yuang-Taung
YT
D004268:DNA-Binding Proteins / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors