In addition to the function they exert in virus replication, viral proteins often strongly interfere with cell physiology by interacting with cellular factors involved in important regulatory networks. Hence, the viral proteins, especially those expressed by DNA or RNA transforming viruses, represent interesting models to better understand cellular regulatory pathways. Along this line, the discovery of the ability of proteins expressed by different viruses to bind various cellular proteins with PSD-95-Discs-large-ZO1 (PDZ) domains has open a new and interesting field of investigation. The PDZ domain is indeed present in many human proteins, as either single or multiple copies, associated or not with other protein domains (for recent reviews see references 4 and 25). The PDZ proteins exert diverse functions, generally having an important organizing role by establishing specific interactions with multiple partners. The archetypal interaction is association of the PDZ domain with the C-terminal end of another protein, with the specificity of the interaction depending on its C-terminal four amino acids and the consensus motif being XS/TXV-COOH for class I PDZ domains (29,32,45). In addition to this general rule, it is now well established that the PDZ domain can also interact with an internal sequence motif and also with another PDZ domain (4, 25). Relying on these properties, PDZ proteins play important roles in transmembrane receptors assembly and clustering, as well as in organization of cellular junctions. This family of proteins also intervenes in signal transduction, and examples of transcriptional regulation activities exist (24, 49). Unexpectedly, it has been observed that three different viral transforming proteins, i.e., E4 open reading frame 1 of adenovirus type 9, E6 of human papillomavirus type 18 (HPV-18), and Tax of human T-cell leukemia virus type 1 (HTLV-1), were able to bind PDZ proteins (31,35,43). These three proteins include a canonical class I PDZ binding site (BS). For E4 and E6, deletion of this C-terminal PDZ BS triggers a loss of in vitro transforming activity (31). The PDZ BS of Tax of HTLV-1 also plays a role in in vitro transformation of Rat-1 cells (23). In line with these observations, it has been observed that a PDZ BS is present at the C terminus of E6 in malignant HPV types, such as HPV-18 or HPV-16, but not in the benign ones, such as . Similarly, Tax of HTLV-2, which is not associated with aggressive leukemia, does not include a functional PDZ BS (23). Collectively, these observations strongly support the notion that a relationship exists between in vivo transformation and interference with the normal functioning of PDZ proteins. Hence, it appears to be important to characterize the complete set of cellular PDZ proteins targeted by these viral oncoproteins. By performing a two-hybrid screen of a human B-lymphocyte cDNA library with Tax as bait, we have previously identified seven different
