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Nature. 2009 Feb 12;457(7231):906-9. doi: 10.1038/nature07575. Epub 2008 Dec 7.

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

Author information

1
Department of Medicine, University of California at San Francisco, 513 Parnassus Avenue, S-1057, San Francisco, California 94143-0451, USA.

Erratum in

  • Nature. 2009 Mar 26;458(7237):538.

Abstract

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.

PMID:
19060883
PMCID:
PMC2642523
DOI:
10.1038/nature07575
[Indexed for MEDLINE]
Free PMC Article

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