Utilization of the CBP but not the p300 co-activator by human T-lymphotropic virus type-2 Tax for p53 inhibition.
We previously reported, both in transfected cells and in human T-cell leukemia virus type-2 subtype B infected cells, that the viral transactivator Tax-2B protein could inhibit p53 functions. We have now investigated the mechanism through which Tax-2B represses p53 using GFPTax-2B fusion proteins. We present evidence that Tax-2B inhibition of p53 function is not linked to CREB/ATF activation, but is uniquely correlated with the interaction of CREB binding protein (CBP), but not p300, with the C-terminus of Tax-2B. Wild type, but not a Tax-2B-M47 mutant, inhibits p53 function in adherent cells. We demonstrate that both Tax-2B and Tax-2B-M47 can bind p300, while Tax-2B-M47 is impaired for CBP binding. Importantly, transfection of increasing amounts of CBP but not p300 or p300/CBP-associated factor (P/CAF) could rescue p53 transcriptional activity in the presence of Tax-2B in nonlymphocytic cells. In lymphoid cells, Tax-2B mediated inhibition of p53 is correlated with the NF-kappaB pathway activation and could be prevented by the overexpression of an IkappaBalpha mutant. Given the similarities between the functional domains of CBP and p300, these results are intriguing and suggest that Tax-2B must bind the CR2 domain of CBP, but not that of p300 in order to repress p53.
Meertens
Laurent
L
Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France.
Pise-Masison
Cynthia
C
Quere
Nelly
N
Brady
John
J
Gessain
Antoine
A
Mahieux
Renaud
R
D050882:CREB-Binding Protein; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D006367:HeLa Cells; D015367:Human T-lymphotropic virus 2 / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*
D016356:Gene Products, tax; D020672:I-kappa B Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D050882:CREB-Binding Protein; C494363:CREBBP protein, human