Genetic evidence of a role for ATM in functional interaction between humanT-cell leukemia virus type 1 Tax and p53

Recent evidence from several investigators suggest that the human T-cell le ukemia virus type 1 Tax oncoprotein represses the transcriptional activity of the tumor suppressor protein, p53. An examination of published findings reveals serious controversy as to the mechanism(s) utilized by Tax to inhib it p53 activity and whether the same mechanism is used by Tax in adherent a nd suspension cells. Here, we have investigated Tax-p53 interaction simulta neously in adherent epithelial (HeLa and Saos) and suspension T-lymphocyte (Jurkat) cells. Our results indicate that Tax activity through the CREB/CRE B-binding protein (CBP), but not NF-kappaB, pathway is needed to repress th e transcriptional activity of p53 in all tested cell lines. However, we did find that while CBP binding by Tax is necessary, it is not sufficient for inhibiting p53 function. Based on knockout cell studies, we correlated a st rong genetic requirement for the ATM, but not protein kinase-dependent DNA, protein in conferring a Tax-p53-repressive phenotype.