ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development.
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.
Oshima
Shigeru
S
Department of Medicine, University of California at San Francisco, 513 Parnassus Avenue, S-1057, San Francisco, California 94143-0451, USA.
Turer
Emre E
EE
Callahan
Joseph A
JA
Chai
Sophia
S
Advincula
Rommel
R
Barrera
Julio
J
Shifrin
Nataliya
N
Lee
Bettina
B
Benedict Yen
T S
TS
Yen
Benjamin
B
Woo
Tammy
T
Malynn
Barbara A
BA
Ma
Averil
A
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D019169:Jurkat Cells; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C514981:NEMO protein, mouse; C503281:Tnip2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D025801:Ubiquitin