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

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


  • Oshima S
  • Turer EE
  • Callahan JA
  • Chai S
  • Advincula R
  • Barrera J
  • Shifrin N
  • Lee B
  • Benedict Yen TS
  • Yen B
  • Woo T
  • Malynn BA
  • Ma A



Publication Data

February 12, 2009

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

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