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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.

Pubmed ID: 10435631


  • De Valck D
  • Jin DY
  • Heyninck K
  • Van de Craen M
  • Contreras R
  • Fiers W
  • Jeang KT
  • Beyaert R



Publication Data

July 22, 1999

Associated Grants


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
  • DNA-Binding Proteins
  • 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