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The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases

Oncogene volume 18, pages 4182–4190 (1999)Cite this article

Abstract

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.

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Acknowledgements

The authors thank S Dewaele for construction of a L929r2 cDNA library, and R Cocquyt and F Molemans for DNA sequencing. We also thank A Meeus and M Van den Hemel for their assistance in performing transient transfections. I Van den Brande and Y Bruynooghe are acknowledged for purification of caspases and technical assistance in performing in vitro caspase assays. Rudi Beyaert is a postdoctoral research assistant with the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen. Research was supported by the Interuniversitaire Attractiepolen, an EC BIOMED2 grant and an EC-TMR grant.

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  1. Dirk De Valck and Dong-Yan Jin: D De Valck and DY Jin have contributed equally to this study

Authors and Affiliations

  1. Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Gent, K.L. Ledeganckstraat 35, B-9000, Gent, Belgium

    Dirk De Valck, Karen Heyninck, Marc Van de Craen, Roland Contreras, Walter Fiers & Rudi Beyaert

  2. Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 306, 9000 Rockville Pike, Bethesda, MD 20892-0460, Maryland, USA

    Dong-Yan Jin & Kuan-Teh Jeang

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De Valck, D., Jin, DY., Heyninck, K. et al. The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases. Oncogene 18, 4182–4190 (1999). https://doi.org/10.1038/sj.onc.1202787

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