論文

査読有り
2016年5月

Differential Involvement of the Npl4 Zinc Finger Domains of SHARPIN and HOIL-1L in Linear Ubiquitin Chain Assembly Complex-Mediated Cell Death Protection

MOLECULAR AND CELLULAR BIOLOGY
  • Satoshi Shimizu
  • ,
  • Hiroaki Fujita
  • ,
  • Yoshiteru Sasaki
  • ,
  • Tatsuaki Tsuruyama
  • ,
  • Kazuhiko Fukuda
  • ,
  • Kazuhiro Iwai

36
10
開始ページ
1569
終了ページ
1583
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1128/MCB.01049-15
出版者・発行元
AMER SOC MICROBIOLOGY

The linear ubiquitin chain assembly complex (LUBAC) participates in NF-kappa B activation and cell death protection. Loss of any of the three LUBAC subunits (catalytic HOIP, accessory HOIL-1L, or accessory SHARPIN subunit) leads to distinct phenotypes in mice and human. cpdm mice (chronic proliferative dermatitis in mice [cpdm]) that lack SHARPIN exhibit chronic inflammatory phenotypes, whereas HOIL-1L knockout mice exhibit no overt phenotypes, despite sharing highly homologous ubiquitin-like (UBL) and Npl4 zinc finger (NZF) domains. Here, we intercrossed mice lacking HOIL-1L and SHARPIN and found that reduction of HOIL-1L in cpdm mice exacerbated inflammatory phenotypes without affecting characteristic features of cpdm disease, whereas reduction of SHARPIN in HOIL-1L knockout mice provoked no overt phenotypes. Hence, loss of SHARPIN and reduction of LUBAC triggers cpdm phenotypes. We found that the NZF domain of SHARPIN, but not that of HOIL-1L, is critical for effective protection from programmed cell death by enhancing the recruitment of LUBAC to the activated TNFR complex. The binding activity to K63-linked ubiquitin chains that the NZF domain of SHARPIN, but not that of HOIL-1L, possesses appears to be involved in the recruitment. Thus, selective recognition of ubiquitin chains by NZFs in LUBAC underlies the regulation of LUBAC function.

Web of Science ® 被引用回数 : 9

リンク情報
DOI
https://doi.org/10.1128/MCB.01049-15
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26976635
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000375233000011&DestApp=WOS_CPL

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