1. Genetic evidence of a role for ATM in functional interaction between human T-cell leukemia virus type 1 Tax and p53
- Author
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Kyong-Wook Yim, Phillip L. Van, Dong-Yan Jin, Kuan-Teh Jeang, George Dapolito, and Akihiro Kurimasa
- Subjects
Immunology ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,DNA-Activated Protein Kinase ,Protein Serine-Threonine Kinases ,Gene Products, tax - physiology ,CREB ,medicine.disease_cause ,Microbiology ,Jurkat cells ,Transformation and Oncogenesis ,Protein-Serine-Threonine Kinases - physiology ,Virology ,medicine ,Humans ,Nuclear protein ,Phosphorylation ,Cyclic AMP Response Element-Binding Protein ,Tumor Suppressor Protein p53 - physiology ,Mutation ,Human T-lymphotropic virus 1 ,biology ,Tumor Suppressor Proteins ,Human T-lymphotropic virus 2 ,Human T-lymphotropic virus 1 - physiology ,NF-kappa B ,Nuclear Proteins ,Gene Products, tax ,biology.organism_classification ,NFKB1 ,Molecular biology ,Cell biology ,DNA-Binding Proteins ,Repressor Proteins ,Cell culture ,Insect Science ,biology.protein ,Tumor Suppressor Protein p53 ,HeLa Cells - Abstract
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-κB, 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., published_or_final_version
- Published
- 2000