p53-mediated Inhibitory Mechanism on HIV-1 Tat is Likely to be Associated with Tat-Phosphorylation.
- Author:
Hee Sun BYUNE
;
Sang Gu LEE
;
Yong Soo BAE
- Publication Type:Original Article
- MeSH:
Animals;
Cats;
Genes, Tumor Suppressor;
HIV-1*;
Humans;
Jurkat Cells;
Phosphorylation;
Plasmids;
Protein Kinases;
RNA Interference;
Trans-Activators;
Transcriptional Activation;
Yeasts
- From:Journal of the Korean Society of Virology
1998;28(1):39-52
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
HIV-1 tat, a strong transactivator, is essential for the HIV-1 replication and AIDS progression. The Tat function is markedly inhibited by human anti-oncogene p53. This work was initiated to identify the p53-associated inhibitory mechanism on tat-mediated transactivation. Inhibitory function of P53 was confirmed by co-transfection of tat-expressing Jurkat cells with LTR-CAT plasmid, or H3Tl cells (LTR-CAT integrated HeLa cells) with different ratio of pSV-tat/pCDNA-p53 plasmids. Results from the direct protein-protein .interaction between soluble p53 and tat, and yeast two-hybrid experiments showed that the co-suppression mechanism is unlikely to be due to the direct interaction. CAT activity was not affected by tat in Jurkat cells which were transfected with p53-promoter-CAT or p53-enhancer-CAT, suggesting that the tat-mediated p53 suppression is not directly associated with p53-promoter. Finally, we have tested protein kinase activity in p53-tranfected Jurkat cells, which might phosphorylate HIV-1 tat, resulting in inhibition of tat function. Some of our data lead us to assume that the p53-mediated tat inhibition is likely to be associated with p53-associated, signaling-mediated phosphorylation of tat, resulting in the dysfunction of tat. This study is now under investigation.
