INHIBITION OF P53 TRANSACTIVATION FUNCTION BY THE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-1 TAX PROTEIN

Citation
Ca. Pisemasison et al., INHIBITION OF P53 TRANSACTIVATION FUNCTION BY THE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-1 TAX PROTEIN, Journal of virology, 72(2), 1998, pp. 1165-1170
Citations number
63
Categorie Soggetti
Virology
Journal title
ISSN journal
0022538X
Volume
72
Issue
2
Year of publication
1998
Pages
1165 - 1170
Database
ISI
SICI code
0022-538X(1998)72:2<1165:IOPTFB>2.0.ZU;2-Z
Abstract
Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent for adult T-cell leukemia. HTLV-1 transforms lymphocytes, and there i s increasing evidence that the virus-encoded protein, Tax, plays a pri mary role in viral transformation, We have shown that wild-type p53 in HTLV-1-transformed cells is stabilized. This study,vas initiated to d irectly analyze whether the p53 in HTLV-1-transformed cell lines,vas t ranscriptionally active and to identify the viral gene product respons ible for stabilization and inactivation. Transfection experiments usin g a p53-responsive reporter plasmid and gamma-irradiation studies demo nstrate that the wild-type p53 in HTLV-1-transformed cell lines is not fully active. Further, we demonstrate that the HTLV-1-transforming pr otein, Tax, stabilizes and inactivates p53 function. Cotransfection of Tax with p53 results in a greater than 10-fold reduction in p53 trans cription activity. Using Gal4-p53 fusion proteins, we demonstrate that Tax inhibition of p53 transactivation function is independent of sequ ence-specific DNA binding. Moreover, Tax inhibits p53 function by inte rfering with the activity of the N-terminal activation domain (amino a cids 1 to 52). We conclude that Tax is involved in the inactivation of p53 function and stabilization of p53 in HTLV-1-infected cells. The f unctional interference of p53 function by Tax may be important for tra nsformation and leukemogenesis.