西亚试剂：ABIN-1 is a ubiquitin sensor that restricts cell death and

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

Shigeru Oshima1,2, Emre E. Turer1,2, Joseph A. Callahan1, Sophia Chai1, Rommel Advincula1, Julio Barrera1, Nataliya Shifrin1, Bettina Lee1, Benjamin Yen1, Tammy Woo1, Barbara A. Malynn1 & Averil Ma1

1 Department of Medicine, University of California at San Francisco, 513 Parnassus Avenue, S-1057, San Francisco, California 94143-0451, USA
2 These authors contributed equally to this work.

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-B) is a novel protein that is thought to inhibit NF-B signalling1, 2. 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.

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