The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases.
A20 is a Cys2/Cys2 zinc finger protein which is induced by a variety of inflammatory stimuli and which has been characterized as an inhibitor of cell death by a yet unknown mechanism. In order to clarify its molecular mechanism of action, we used the yeast two-hybrid system to screen for ... proteins that interact with A20. A cDNA fragment was isolated which encoded a portion of a novel protein (TXBP151), which was recently found to be a human T-cell leukemia virus type-I (HTLV-I) Tax-binding protein. The full-length 2386 bp TXBP151 mRNA encodes a protein of 86 kDa. Like A20, overexpression of TXBP151 could inhibit apoptosis induced by tumour necrosis factor (TNF) in NIH3T3 cells. Moreover, transfection of antisense TXBP151 partially abolished the anti-apoptotic effect of A20. Furthermore, apoptosis induced by TNF or CD95 (Fas/APO-1) was associated with proteolysis of TXBP151. This degradation could be inhibited by the broad-spectrum caspase inhibitor zVAD-fmk or by expression of the cowpox virus-derived inhibitor CrmA, suggesting that TXBP151 is a novel substrate for caspase family members. TXBP151 was indeed found to be specifically cleaved in vitro by members of the caspase-3-like subfamily, viz. caspase-3, caspase-6 and caspase-7. Thus TXBP151 appears to be a novel A20-binding protein which might mediate the anti-apoptotic activity of A20, and which can be processed by specific caspases.
Mesh Terms:
3T3 Cells, Amino Acid Chloromethyl Ketones, Amino Acid Sequence, Animals, Antigens, CD95, Apoptosis, Base Sequence, Carrier Proteins, Caspases, Cell Line, Cloning, Molecular, Cysteine Endopeptidases, Cysteine Proteinase Inhibitors, DNA, Complementary, Dactinomycin, Genes, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Neoplasm Proteins, Nuclear Proteins, Nucleic Acid Synthesis Inhibitors, Oligonucleotides, Antisense, Protein Binding, Protein Processing, Post-Translational, Proteins, RNA, Messenger, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Serpins, Substrate Specificity, Transfection, Tumor Necrosis Factor-alpha, Viral Proteins, Zinc Fingers
3T3 Cells, Amino Acid Chloromethyl Ketones, Amino Acid Sequence, Animals, Antigens, CD95, Apoptosis, Base Sequence, Carrier Proteins, Caspases, Cell Line, Cloning, Molecular, Cysteine Endopeptidases, Cysteine Proteinase Inhibitors, DNA, Complementary, Dactinomycin, Genes, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Neoplasm Proteins, Nuclear Proteins, Nucleic Acid Synthesis Inhibitors, Oligonucleotides, Antisense, Protein Binding, Protein Processing, Post-Translational, Proteins, RNA, Messenger, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Serpins, Substrate Specificity, Transfection, Tumor Necrosis Factor-alpha, Viral Proteins, Zinc Fingers
Oncogene
Date: Jul. 22, 1999
PubMed ID: 10435631
View in: Pubmed Google Scholar
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