Genetic evidence of a role for ATM in functional interaction between human T-cell leukemia virus type 1 Tax and p53.
Recent evidence from several investigators suggest that the human T-cell leukemia 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 inhibit p53 activity and whether the same mechanism is used by Tax in adherent and suspension cells. Here, we have investigated Tax-p53 interaction simultaneously in adherent epithelial (HeLa and Saos) and suspension T-lymphocyte (Jurkat) cells. Our results indicate that Tax activity through the CREB/CREB-binding protein (CBP), but not NF-kappaB, pathway is needed to repress the 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 strong genetic requirement for the ATM, but not protein kinase-dependent DNA, protein in conferring a Tax-p53-repressive phenotype.
Van
P L
PL
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Yim
K W
KW
Jin
D Y
DY
Dapolito
G
G
Kurimasa
A
A
Jeang
K T
KT
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D016356:Gene Products, tax / Q000502:physiology*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D015367:Human T-lymphotropic virus 2 / Q000502:physiology; D006801:Humans; D009154:Mutation; D016328:NF-kappa B / Q000502:physiology; D009687:Nuclear Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D016328:NF-kappa B; D009687:Nuclear Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases