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Activation of the Ets Transcription Factor Elf‐1 Requires Phosphorylation and Glycosylation
Author(s) -
TSOKOS GEORGE C.,
NAMBIAR MADHUSOODANA P.,
JUANG YUANGTAUNG
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb06054.x
Subject(s) - jurkat cells , transcription factor , phosphorylation , transcription (linguistics) , microbiology and biotechnology , t cell receptor , gene , biology , ets transcription factor family , promoter , chemistry , gene expression , t cell , genetics , linguistics , philosophy , immune system
A bstract : 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 ϑ, 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 ζ 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) ζ 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 ζ 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.