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

Shigeru Oshima, Emre E. Turer, Joseph A. Callahan, Sophia Chai, Rommel Advincula, Julio Barrera, Nataliya Shifrin, Bettina Lee, Benjamin Yen, Tammy Woo, Barbara A. Malynn, Averil Ma

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

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-κB) is a novel protein that is thought to inhibit NF-κB 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.

Original languageEnglish (US)
Pages (from-to)906-909
Number of pages4
JournalNature
Volume457
Issue number7231
DOIs
StatePublished - Feb 12 2009

ASJC Scopus subject areas

  • General

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