A TNF- and c-Cbl-dependent FLIPS-degradation pathway and its function in Mycobacterium tuberculosis-induced macrophage apoptosis

Manikuntala Kundu, Sushil Kumar Pathak, Kuldeep Kumawat, Sanchita Basu, Gargi Chatterjee, Shresh Pathak, Takuya Noguchi, Kohsuke Takeda, Hidenori Ichijo, Christine B.F. Thien, Wallace Y. Langdon, Joyoti Basu

研究成果: Article査読

57 被引用数 (Scopus)

抄録

Apoptosis is central to the interaction between pathogenic mycobacteria and host macrophages. Caspase-8-dependent apoptosis of infected macrophages, which requires activation of the mitogen-activated protein (MAP) kinase p38, lowers the spread of mycobacteria. Here we establish a link between the release of tumor necrosis factor (TNF) and mycobacteria-mediated macrophage apoptosis. TNF activated a pathway involving the kinases ASK1, p38 and c-Abl. This pathway led to phosphorylation of FLIPS, which facilitated its interaction with the E3 ubiquitin ligase c-Cbl. This interaction triggered proteasomal degradation of FLIPS, which promoted activation of caspase-8 and apoptosis. Our findings identify a previously unappreciated signaling pathway needed for Mycobacterium tuberculosis-triggered macrophage cell death.

本文言語English
ページ(範囲)918-926
ページ数9
ジャーナルNature Immunology
10
8
DOI
出版ステータスPublished - 2009
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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