Nuclear factor-90 of activated T-cells: A double-stranded RNA-binding protein and substrate for the double-stranded RNA-dependent protein kinase, PKR.
NFAT transcription factors play a central role in initiating T-cell activation through the induction of immediate-early T-cell specific genes including interleukin-2 (IL-2). NFAT transcription factors bind to a sequence in the IL-2 enhancer known as the antigen receptor response element 2 (ARRE-2). Multiple proteins exhibiting ARRE-2 binding activity have been isolated, including a heterodimer from stimulated T-cell nuclear extracts consisting of Mr = 90 000 (NF90) and Mr = 45 000 (NF45) subunits. The subunits of this heterodimer have been cloned, and NF90 was found to encode a protein containing two domains that are predicted to form motifs capable of binding to double-stranded RNA. Using in vitro translated polypeptides, we have demonstrated that NF90 specifically binds to double-stranded RNA. Furthermore, NF90 was phosphorylated in a double-stranded RNA-dependent manner likely by the interferon-induced, double-stranded RNA-dependent protein kinase, PKR. The NF90 protein was found to be expressed not only in T-cells, but also in nonimmune HeLa cells. In HeLa cells, the protein was almost exclusively localized to the ribosome salt wash fraction of cell lysates.
D000595:Amino Acid Sequence; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D051903:Nuclear Factor 45 Protein; D050779:Nuclear Factor 90 Proteins; D009687:Nuclear Proteins; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D019892:eIF-2 Kinase / Q000378:metabolism*