title: Dominant expression of a novel splice variant of caspase-8 in human peripheral blood lymphocytes.
abstract: Caspase-8 is an apical and critical proteolytic enzyme in the cascade of apoptosis. As a result of alternative splicing, the generation of at least 7 isoforms of caspase-8 has been reported. The existence of multiple isoforms that lack the essential domains for apoptosis suggests the possible role of these isoforms on the regulation of apoptosis. Here we report a novel longer isoform of caspase-8 (caspase-8L) that was generated by alternative splicing of intron 8, thereby carrying a 136-bp insertion and frame shift of the transcript. The transcript encoded N-terminal two repeats of death effector domain (DED) of caspase-8, but lacking the C-terminal half of the proteolytic domain. Reverse transcriptase (RT)-polymerase chain reaction (PCR) analysis revealed the dominant expression of caspase-8L transcript compared to the intact form of caspase-8 in human peripheral blood lymphocyte (PBL) and T cells. In patients with systemic lupus erythematosus (SLE), imbalanced expression of caspase-8L transcript was identified. These results suggest the important role of caspase-8L in the modulation of apoptosis.
authors.affiliation: Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. horiuchi@intmed1.med.kyushu-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Horiuchi
authors.forename: D
authors.initials: D
authors.lastname: Himeji
authors.forename: H
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: S
authors.initials: S
authors.lastname: Harashima
authors.forename: C
authors.initials: C
authors.lastname: Hashimura
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry / Q000235:genetics*; D020134:Catalytic Domain; D002478:Cells, Cultured; D005091:Exons / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases