The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins

被引:161
作者
Rousset, R [1 ]
Fabre, S [1 ]
Desbois, C [1 ]
Bantignies, F [1 ]
Jalinot, P [1 ]
机构
[1] Ecole Normale Super Lyon, Lab Biol Mol & Cellulaire, CNRS, UMR 49, F-69364 Lyon 07, France
关键词
HTLV-1; Tax; PDZY; two-hybrid;
D O I
10.1038/sj.onc.1201567
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Infection by HTLV-1 has been correlated with the appearance of various proliferative or degenerative diseases. Some of these disorders have been observed in transgenic mice expressing the Tax protein, which is known to transactivate various viral and cellular promoters through interactions with several transcription factors. In this study we show that the C-terminus of this viral oncoprotein represents a motif permitting binding of Tax to the PDZ domains of several cellular proteins. A two-hybrid screen with Tax as bait indeed yielded complementary DNAs coding for six proteins including PDZ domains. Two of them correspond to truncated forms of the PSD-95 and beta 1-syntrophin proteins, another clone codes for a protein homologous to the product of the C. elegans gene lin-7. The other three clones code for new human members of the PDZ family of cellular proteins. The interaction of Tax with the products of these clones was confirmed by immunoprecipitation assays in mammalian cells, and analysis of various mutants of Tax established the importance of the C-terminal amino acids for several of these interactions. These data suggest that Tax could perturb the normal function of targeted cellular proteins by strongly interacting with their PDZ domains.
引用
收藏
页码:643 / 654
页数:12
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