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Article (Scientific journals)
Structure of the human APO-1 gene
Behrmann, Iris; Walczak, H.; Krammer, P. H.
1995In European Journal of Immunology, 24 (12), p. 3057-62
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Keywords :
Amino Acid Sequence; Transcription Factors; Restriction Mapping; RNA, Messenger; RNA Splicing; Promoter Regions (Genetics); Molecular Sequence Data; Humans; Genes; Gene Expression Regulation; Cloning, Molecular; Binding Sites; Base Sequence; Antigens, Surface; Antigens, CD95; Transcription, Genetic
Abstract :
[en] APO-1/Fas (CD95) is a type 1 transmembrane protein that belongs to the tumor necrosis factor/nerve growth factor receptor family characterized by cysteine-rich extracellular domains. Cross-linking of APO-1 mediates apoptosis in a variety of cells. In the present study we report the isolation and characterization of the human APO-1 gene spanning approximately 25 kb of human chromosome 10. The gene consists of nine exons (25 bp to > 1.44 kb) separated by eight introns (152 bp to approximately 12 kb). The boundaries of exon 2 to 5 encoding the extracellular region do not match the boundaries of the three APO-1 protein subdomains. Exon structure and functional protein domains correspond for exon 6 encoding the transmembrane region and for exon 9 encoding the "death domain". By a polymerase chain reaction-based approach we localized major transcriptional start sites in human spleen cells 77 and 73 nucleotides upstream of the translation initiation codon of the human APO-1 gene. Minor initiation sites were found at positions -128, -111, -91, and -74. The 5' flanking sequence of the human APO-1 gene is GC rich, contains a high number of CpG dinucleotides and lacks a consensus TATA box. Consensus binding sites for the transcription factors Sp1, AP-1, AP-2, GAF, NF-kappa B, and NF-AT were found. The elucidation of the human APO-1 gene structure will facilitate the study of its involvement in various diseases such as in autoimmunity.
Disciplines :
Biochemistry, biophysics & molecular biology
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Author, co-author :
Behrmann, Iris ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Walczak, H.
Krammer, P. H.
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Title :
Structure of the human APO-1 gene
Publication date :
Journal title :
European Journal of Immunology
Publisher :
VCH Verlagsgesellschaft, Weinheim, Germany
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Peer reviewed :
Peer reviewed
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