美國加州大學(xué)舊金山分校醫(yī)學(xué)院的研究人員在最新一期Nature雜志上發(fā)表關(guān)于泛素化受體ABIN-1的研究性文章，該文章揭示了ABIN-1的生理功能,，它具有限制細(xì)胞死亡以及維持胚胎發(fā)育的功能,。
ABIN-1（A20 binding and inhibitor of NF-kB ）是一個新發(fā)現(xiàn)的蛋白，具有抑制NF-kB的功能,。通過研究ABIN-1的功能,，Aberil研究小組發(fā)現(xiàn)，小鼠如果通過遺傳技術(shù)將ABIN-1剔除將會導(dǎo)致嚴(yán)重的后果,，其在胚胎發(fā)育過程中會出現(xiàn)以下癥狀,，肝臟自我壞死，貧血和發(fā)育不全，并因此而死亡,。研究發(fā)現(xiàn)缺乏ABIN-1的細(xì)胞對腫瘤壞死因子（TNF）高度敏感,，導(dǎo)致細(xì)胞進(jìn)入凋亡程序；然而,，如果細(xì)胞在缺乏ABIN-1的同時也缺乏TNF則不會受到致死性的影響,，胚胎就能存活下來。ABIN-1能抑制TNF信號通路中Caspase8的補充FADD的作用,。ABIN-1在直接結(jié)合到多聚泛素鏈上,，然后啟動泛素化傳感活性。
這項研究成果顯示了泛素與泛素肽傳感蛋白具有調(diào)控細(xì)胞和器官維持正常生命機能的作用,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 457, 906-909 (12 February 2009) | doi:10.1038/nature07575
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.
