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

Article

关键词: NF-KAPPA-B;    ZINC-FINGER PROTEIN;    JNK ACTIVATION;    MICE;    A20;    INDUCTION;    LETHALITY;    APOPTOSIS;    RESPONSES;    REQUIRES;   

DOI  :  10.1038/nature07575

来源: SCIE

【 摘 要 】

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-kappa B) is a novel protein that is thought to inhibit NF-kappa B signalling(1,2). 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.

【 授权许可】

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