Reference : Structure of the human APO-1 gene
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Structure of the human APO-1 gene
Behrmann, Iris mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Walczak, H. [> >]
Krammer, P. H. [> >]
European Journal of Immunology
VCH Verlagsgesellschaft
Yes (verified by ORBilu)
[en] 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
[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.

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