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ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development.

Nature | Feb 12, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19060883

Proteins that directly regulate tumour necrosis factor receptor (TNFR) signalling have critical roles in regulating cellular activation and survival. ABIN-1 (A20 binding and inhibitor of NF-kappaB) is a novel protein that is thought to inhibit NF-kappaB signalling. Here we show that mice deficient for ABIN-1 die during embryogenesis with fetal liver apoptosis, anaemia and hypoplasia. ABIN-1 deficient cells are hypersensitive to tumour necrosis factor (TNF)-induced programmed cell death, and TNF deficiency rescues ABIN-1 deficient embryos. ABIN-1 inhibits caspase 8 recruitment to FADD (Fas-associated death domain-containing protein) in TNF-induced signalling complexes, preventing caspase 8 cleavage and programmed cell death. Moreover, ABIN-1 directly binds polyubiquitin chains and this ubiquitin sensing activity is required for ABIN-1's anti-apoptotic activity. These studies provide insights into how ubiquitination and ubiquitin sensing proteins regulate cellular and organismal survival.

Pubmed ID: 19060883 RIS Download

Mesh terms: Adaptor Proteins, Signal Transducing | Amino Acid Sequence | Animals | Apoptosis | Cell Line | DNA-Binding Proteins | Embryonic Development | Gene Expression Regulation, Developmental | Humans | Intracellular Signaling Peptides and Proteins | Jurkat Cells | Mice | Mice, Knockout | Molecular Sequence Data | Sequence Alignment | Tumor Necrosis Factor-alpha | Ubiquitin

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Associated grants

  • Agency: NIDDK NIH HHS, Id: R01 DK071939
  • Agency: NIDDK NIH HHS, Id: R01 DK071939-01
  • Agency: NIDDK NIH HHS, Id: R01 DK071939-02
  • Agency: NIDDK NIH HHS, Id: R01 DK071939-03
  • Agency: NIDDK NIH HHS, Id: R01 DK071939-04

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