Defective production of functional 98-kDa form of Elf-1 is responsible for the decreased expression of TCR zeta-chain in patients with systemic lupus erythematosus. Journal of immunology (Baltimore, Md. : 1950) [J Immunol] Journal article | | Title | Defective production of functional 98-kDa form of Elf-1 is responsible for the decreased expression of TCR zeta-chain in patients with systemic lupus erythematosus. | | Author(s) | Juang YT, Tenbrock K, Nambiar MP, Gourley MF, Tsokos GC | | Institution | Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Yuang-Taung.Juang@NA.AMEDD.ARMY.MIL | | Source | J Immunol 2002 Nov 15; 169(10):6048-55. | | MeSH | Adult
Aged
Aged, 80 and over
DNA-Binding Proteins
Down-Regulation
Ephrin-A2
Female
Gene Expression Regulation
Humans
Isoelectric Point
Lupus Erythematosus, Systemic
Male
Membrane Proteins
Middle Aged
Molecular Weight
Nuclear Proteins
Promoter Regions (Genetics)
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-ets
RNA, Messenger
Receptors, Antigen, T-Cell
Research Support, U.S. Gov't, P.H.S.
T-Lymphocyte Subsets
Transcription Factors
| | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 12421992 |
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