title: Multiple NF-ATc isoforms with individual transcriptional properties are synthesized in T lymphocytes.
abstract: The transcription factor NF-ATc that controls gene expression in T lymphocytes and embryonic cardiac cells is expressed in three prominent isoforms. This is due to alternative splice/polyadenylation events that lead to the predominant synthesis of two long isoforms in naive T cells and a shorter NF-ATc isoform in effector T cells. Whereas the previously described isoform NF-ATc/A contains a relatively short C terminus, the longer isoforms, B and C, span extra C-terminal peptides of 128 and 246 aa, respectively. We show here that in addition to the strong N-terminal trans-activation domain, TAD-A, which is common to all three NF-ATc isoforms, NF-ATc/C contains a second trans-activation domain, TAD-B, in its C-terminal peptide. Various stimuli of T cells that induce the activity of TAD-A also enhance the activity of TAD-B, but, unlike TAD-A, TAD-B remains unphosphorylated by protein from 12-O-tetradecanoyl 12-phorbol 13-acetate-stimulated T cells. The shorter C-terminal peptide of isoform NF-ATc/B exerts a suppressive transcriptional effect. These properties of NF-ATc/B and -C might be of importance for gene regulation in naive T lymphocytes in which NF-ATc/B and -C are predominantly synthesized.
authors.affiliation: Department of Molecular Pathology, Institute of Pathology, University of Würzburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Chuvpilo
authors.forename: A
authors.initials: A
authors.lastname: Avots
authors.forename: F
authors.initials: F
authors.lastname: Berberich-Siebelt
authors.forename: J
authors.initials: J
authors.lastname: Glöckner
authors.forename: C
authors.initials: C
authors.lastname: Fischer
authors.forename: A
authors.initials: A
authors.lastname: Kerstan
authors.forename: C
authors.initials: C
authors.lastname: Escher
authors.forename: I
authors.initials: I
authors.lastname: Inashkina
authors.forename: F
authors.initials: F
authors.lastname: Hlubek
authors.forename: E
authors.initials: E
authors.lastname: Jankevics
authors.forename: T
authors.initials: T
authors.lastname: Brabletz
authors.forename: E
authors.initials: E
authors.lastname: Serfling
mesh_terms: D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000096:biosynthesis; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology*; D015533:Transcriptional Activation / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D008222:Lymphokines; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D009687:Nuclear Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; D014157:Transcription Factors; D013755:Tetradecanoylphorbol Acetate