The Role of NF-kappaB RelA Subunit for Tax-inhibition of p53 Transcriptional Activity in Human T-cell Lymphotrophic Virus Type 1.
- Author:
Soo Jin JEONG
1
;
Jae Dong LEE
;
Min Ho JEONG
Author Information
1. Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, USA.
- Publication Type:Original Article
- Keywords:
HTLV-1;
Tax;
NF-kappaB;
RelA;
p53
- MeSH:
Cell Line;
Genome;
Human T-lymphotropic virus 1;
Humans*;
Immunoprecipitation;
Leukemia;
Leukemia-Lymphoma, Adult T-Cell;
NF-kappa B*;
Oligonucleotides;
Oligonucleotides, Antisense;
T-Lymphocytes*;
Taxes;
Transcriptional Activation
- From:Journal of Bacteriology and Virology
2004;34(3):231-237
- CountryRepublic of Korea
- Language:English
-
Abstract:
Human T-cell lymphotrophic virus type I (HTLV-I) is a causative agent of adult T-cell leukemia (ATL). The viral transcriptional activator Tax encoded by the HTLV-I genome is thought to play critical roles in the activation of nuclear factor kappaB(NF-kappaB) as well as in the transformation of human T lymphocytes and the induction of tumor and leukemia. In this report, we suggest that RelA subunit of NF-kappaB might play an important role in Tax-induced p53 inactivation. Using antisense oligonucleotides, the ability of Tax inhibiting p53 transactivation was blocked by RelA, but not p50 or c-rel, antisense oligonucleotides in C81 HTLV-1-transfected cell line. The inability of p50 or c-rel antisense oligonucleotides in blocking the Tax-mediated inhibition of p53 function was not due lack of activity, since NF-kappaB activation was specifically blocked by these oligonucleotides. Also, we demonstrate by using co-immunoprecipitation assays that p53 interacts with RelA in HTLV-I transformed cells and their binding became stronger by the overexpression of Tax in 293T cells. These results suggest the possibility that the physical interaction between p53 and RelA correlates with Tax-induced p53 inhibition.
