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Mind bomb 1 regulation of cFLIP interactions.

http://www.ncbi.nlm.nih.gov/pubmed/19710364

Mind bomb 1 (Mib1) is a multidomain E3 ligase that directs ubiquitination of the Notch ligands Delta and Jagged to promote their endocytosis. Here we examine Notch-independent functions of Mib1 and find that its activities are linked to the initiation of the extrinsic cell death pathway. Expression of Mib1 induces a spontaneous, caspase-dependent cell death. Consistent with this, depletion of endogenous Mib1 decreases tumor-necrosis factor (TNF)-induced cell death. Mib1 was found to bind to cellular Fas-associated death domain (FADD)-like IL-1b converting enzyme (FLICE)-like inhibitory proteins (cFLIP-L and cFLIP-S), whereas only cFLIP-s can inhibit Mib1-induced cell death. The interaction between Mib1 and cFLIP decreases the association of caspase-8 with cFLIP, which activates caspase-8 and induces cell death. Collectively, these results suggest that in addition to a central role in Notch signaling, Mib1 has an important role in regulating the extrinsic cell death pathway.

Pubmed ID: 19710364 RIS Download

Mesh terms: Apoptosis | Blotting, Western | CASP8 and FADD-Like Apoptosis Regulating Protein | Caspase 8 | Cell Line | Humans | Immunoprecipitation | Signal Transduction | Ubiquitin-Protein Ligases | Ubiquitination

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Associated grants

  • Agency: NIDDK NIH HHS, Id: DK-062810
  • Agency: NHLBI NIH HHS, Id: HL-54118
  • Agency: NIDDK NIH HHS, Id: R01 DK062810
  • Agency: NIDDK NIH HHS, Id: R01 DK062810-05
  • Agency: NHLBI NIH HHS, Id: R01 HL054118
  • Agency: NHLBI NIH HHS, Id: R01 HL054118-08

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