Defective production of functional 98-kDa form of Elf-1 is responsible for the decreased expression of TCR ζ-chain in patients with systemic lupus erythematosus

YT Juang, K Tenbrock, MP Nambiar… - The Journal of …, 2002 - journals.aai.org
YT Juang, K Tenbrock, MP Nambiar, MF Gourley, GC Tsokos
The Journal of Immunology, 2002journals.aai.org
Systemic lupus erythematosus (SLE), the prototypic autoimmune disease, is characterized
by defective expression of TCR ζ-chain. Elf-1 (E-74-like factor) is a member of the Ets (E-26-
specific) family and is crucial for the basal transcription of TCR ζ-chain in Jurkat cells. We
previously demonstrated that Elf-1 exists in the cytoplasm mainly as 80-kDa form and after
phosphorylation and O-glycosylation it moves to the nucleus as a 98-kDa which binds DNA.
We now demonstrate that Elf-1 is crucial for the transactivation of TCR ζ-chain promoter in …
Abstract
Systemic lupus erythematosus (SLE), the prototypic autoimmune disease, is characterized by defective expression of TCR ζ-chain. Elf-1 (E-74-like factor) is a member of the Ets (E-26-specific) family and is crucial for the basal transcription of TCR ζ-chain in Jurkat cells. We previously demonstrated that Elf-1 exists in the cytoplasm mainly as 80-kDa form and after phosphorylation and O-glycosylation it moves to the nucleus as a 98-kDa which binds DNA. We now demonstrate that Elf-1 is crucial for the transactivation of TCR ζ-chain promoter in normal and SLE T cells. Defective expression of TCR ζ-chain in SLE T cells is associated with two distinct molecular defects in the generation of the 98-kDa DNA binding Elf-1 form. In the first, the levels of the 98-kDa form were either decreased or absent. In the second, the apparent levels of the nuclear Elf-1 form were normal but included only two of the three bands into which the nuclear Elf-1 form separated in isoelectric focusing gels. Because both the transcription and the translation processes of Elf-1 gene are normal in SLE T cells, our data demonstrate that abnormal posttranslational mechanisms of the Elf-1 protein result in defective expression of functional Elf-1, and consequently, the transcriptional defect of TCR ζ-chain in patients of SLE.
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