ブタcellular FLICE-like inhibitory protein遺伝子のクローニングと発現解析 Porcine (Sus scrofa) Cellular FLICE-like Inhibitory Protein (cFLIP) : Molecular Cloning and Comparison with the Human and Murine cFLIP

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Abstract

選択的な卵胞閉鎖を支配的に調節している顆粒層細胞アポトーシスの分子制御機構を解明する一環として、細胞死受容体を介した細胞内アポトーシスシグナルの伝達を抑制するブタのcFLIP遺伝子をクローニングした。ブタ卵胞顆粒層細胞cDNAライブラリーから選択的スプライシングによって生じる2種のアイソフォーム(long form:cFLIP(L)およびshor form:cFLIP(S))を同定した。これらはヒトおよびマウスと高い相同性を示した。どちらもそのN末端側に二連のdeah effecor domain(DED)を有し、他のシグナル伝達因子とこれらを介して結合することでアポトーシスシグナル伝達を阻害すると考えられた。cFLIP(S)のC末端は短かったが、cFLIP(L)はカスパーゼ様領域を持っていた。R-PCR解析によると、健常卵胞顆粒層細胞では両cFLIPアイソフォームとも強く発現していた。これらの所見からcFLIPはブタ卵巣顆粒層細胞におけるアポトーシス制御に重要な役割を果たしていることが推察された。

To reveal the molecular regulation mechanism of selective follicular atresia in porcine ovaries, we isolated the porcine cDNA encoding cellular FLICE-like inhibitory protein (cFLIP), which inhibits death receptor-mediated apoptosis signal transduction. Two alternative splicing isoforms of cFLIP, porcine cellular FLIP-short form (pcFLIP<sub>S</sub>, 642 bp and 214-aa) and -long form (pcFLIP<sub>L</sub>, 1446 bp and 482-aa), were identified from a cDNA library prepared from follicular granulosa cells of pig ovaries. pcFLIP<sub>S</sub> and pcFLIP<sub>L</sub> indicated high identities with human and murine cFLIP, and both of them contain two tandem specific amino acid regions (death effector domain: DED) in their N-terminal, suggesting that pcFLIP<sub>S</sub> and pcFLIP<sub>L</sub> inhibit the death receptor-mediated apoptosis signal by binding to other pro-apoptotic factors mediated by DED. pcFLIP<sub>S</sub> contains a short C-terminal region, while pcFLIP<sub>L</sub> has a caspase-like domain in the C-terminal region. The reverse transcription-polymerase chain reaction analysis revealed that both pcFLIP<sub>S</sub> and pcFLIP<sub>L</sub> mRNAs were highly expressed in granulosa cells of healthy follicles, suggesting that these cFLIPs play important roles in the regulation mechanism of apoptosis in ovarian follicular granulosa cells. The present data will contribute to understanding of the physiological roles of cFLIPs in the apoptosis regulation in porcine tissues.<br>

Journal

  • Journal of Reproduction and Development

    Journal of Reproduction and Development 50(5), 549-555, 2004-10-01

    Japanese Society of Animal Reproduction

References:  18

Cited by:  12

Codes

  • NII Article ID (NAID)
    10027323381
  • NII NACSIS-CAT ID (NCID)
    AA10936678
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09168818
  • NDL Article ID
    7116704
  • NDL Source Classification
    ZR22(科学技術--農林水産--畜産)
  • NDL Call No.
    Z54-H305
  • Data Source
    CJP  CJPref  NDL  J-STAGE  JASI 
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