Abstract
Systemic lupus erythematosus (SLE), the prototypic autoimmune disease, is characterized by defective expression of TCR zeta-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 zeta-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 zeta-chain promoter in normal and SLE T cells. Defective expression of TCR zeta-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 zeta-chain in patients of SLE.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / metabolism
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Down-Regulation / genetics
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Down-Regulation / immunology*
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Ephrin-A2 / biosynthesis*
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Ephrin-A2 / deficiency
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Ephrin-A2 / metabolism
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Ephrin-A2 / physiology
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Female
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology
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Humans
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Isoelectric Point
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Lupus Erythematosus, Systemic / genetics
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Lupus Erythematosus, Systemic / immunology*
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Lupus Erythematosus, Systemic / metabolism*
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Lupus Erythematosus, Systemic / pathology
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Male
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / biosynthesis*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Middle Aged
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Molecular Weight
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / deficiency
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Nuclear Proteins / metabolism
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Promoter Regions, Genetic / immunology
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-ets
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / biosynthesis
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Receptors, Antigen, T-Cell / antagonists & inhibitors
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Receptors, Antigen, T-Cell / biosynthesis*
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / pathology
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Transcription Factors / biosynthesis
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Transcription Factors / deficiency
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Transcription Factors / physiology
Substances
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DNA-Binding Proteins
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Ephrin-A2
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Membrane Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-ets
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RNA, Messenger
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Receptors, Antigen, T-Cell
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Transcription Factors
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antigen T cell receptor, zeta chain