본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

The Journal of biological chemistry v.292 no.4, 2017년, pp.1218 - 1230   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

A Disease-associated Mutant of NLRC4 Shows Enhanced Interaction with SUG1 Leading to Constitutive FADD-dependent Caspase-8 Activation and Cell Death

Raghawan, Akhouri Kishore (From the CSIR–Centre for Cellular and Molecular Biology, Hyderabad 500007, India ); Sripada, Anand (From the CSIR–Centre for Cellular and Molecular Biology, Hyderabad 500007, India ); Gopinath, Gayathri (From the CSIR–Centre for Cellular and Molecular Biology, Hyderabad 500007, India ); Pushpanjali, Pendyala (From the CSIR–Centre for Cellular and Molecular Biology, Hyderabad 500007, India ); Kumar, Yatender (From the CSIR–Centre for Cellular and Molecular Biology, Hyderabad 500007, India ); Radha, Vegesna (From the CSIR–Centre for Cellular and Molecular Biology, Hyderabad 500007, India ); Swarup, Ghanshyam (From the CSIR–Centre for Cellular and Molecular Biology, Hyderabad 500007, India );
  • 초록  

    Nod-like receptor family card containing 4 (NLRC4)/Ipaf is involved in recognition of pathogen-associated molecular patterns leading to caspase-1 activation and cytokine release, which mediate protective innate immune response. Point mutations in NLRC4 cause autoinflammatory syndromes. Although all the mutations result in constitutive caspase-1 activation, their phenotypic presentations are different, implying that these mutations cause different alterations in properties of NLRC4. NLRC4 interacts with SUG1 and induces caspase-8-mediated cell death. Here, we show that one of the autoinflammatory syndrome-causing mutants of NLRC4, H443P, but not T337A and V341A, constitutively activates caspase-8 and induces apoptotic cell death in human lung epithelial cells. Compared with wild type NLRC4, the H443P mutant shows stronger interaction with SUG1 and with ubiquitinated cellular proteins. Phosphorylation of NLRC4 at Ser 533 plays a crucial role in caspase-8 activation and cell death. However, H443P mutant does not require Ser 533 phosphorylation for caspase-8 activation and cell death. Caspase-8 activation by NLRC4 and its H443P mutant are dependent on the adaptor protein FADD. A phosphomimicking mutant of NLRC4, S533D does not require SUG1 activity for inducing cell death. Ubiquitin-tagged NLRC4 could induce cell death and activate caspase-8 independent of Ser 533 phosphorylation. Our work suggests that SUG1-mediated signaling results in enhanced ubiquitination and regulates FADD-dependent caspase-8 activation by NLRC4. We show that the autoinflammation-associated H443P mutant is altered in interaction with SUG1 and ubiquitinated proteins, triggering constitutive caspase-8-mediated cell death dependent on FADD but independent of Ser 533 phosphorylation.


  • 주제어

    apoptosis .   caspase .   cell death .   inflammasome .   phosphorylation .   ubiquitylation (ubiquitination).  

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • 원문이 없습니다.
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기