Differential Role of PKC-Induced c-Jun in HTLV-1 LTR Activation by 12-O-Tetradecanoylphorbol-13-acetate in Different Human T-cell Lines
| Autor: | W T Godbey, Ammar Abou-Kandil, Rachel Chamias, Mordechai Aboud, Mahmoud Huleihel |
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| Rok vydání: | 2012 |
| Předmět: |
Cell type
Proto-Oncogene Proteins c-jun T-Lymphocytes viruses T cell lcsh:Medicine Gene Expression Biology Response Elements 12-O-Tetradecanoylphorbol-13-acetate Biochemistry Microbiology Jurkat cells Gene Expression Regulation Enzymologic Cell Line Jurkat Cells chemistry.chemical_compound Downregulation and upregulation Virology Molecular Cell Biology Genetics medicine Humans Phosphorylation RNA Small Interfering lcsh:Science Protein Kinase C Human T-lymphotropic virus 1 Binding Sites Multidisciplinary lcsh:R c-jun Terminal Repeat Sequences Proteins Molecular biology Viral Replication Isoenzymes Viral Classification medicine.anatomical_structure chemistry Cell culture Tetradecanoylphorbol Acetate lcsh:Q Protein Binding Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 1, p e29934 (2012) |
| ISSN: | 1932-6203 |
| Popis: | We have previously shown that TPA activates HTLV-1 LTR in Jurkat T-cells by inducing the binding of Sp1-p53 complex to the Sp1 site residing within the Ets responsive region 1 (ERR-1) of the LTR and that this activation is inhibited by PKCalpha and PKCepsilon. However, in H9 T-cells TPA has been noted to activate the LTR in two consecutive stages. The first stage is activation is mediated by PKCetta and requires the three 21 bp TRE repeats. The second activation mode resembles that of Jurkat cells, except that it is inhibited by PKCdelta. The present study revealed that the first LTR activation in H9 cells resulted from PKCetta-induced elevation of non-phosphorylated c-Jun which bound to the AP-1 site residing within each TRE. In contrast, this TRE-dependent activation did not occur in Jurkat cells, since there was no elevation of non-phosphorylated c-Jun in these cells. However, we found that PKCalpha and PKCepsilon, in Jurkat cells, and PKCetta and PKCdelta, in H9 cells, increased the level of phosphorylated c-Jun that interacted with the Sp1-p53 complex. This interaction prevented the Sp1-p53 binding to ERR-1 and blocked, thereby, the ERR-1-mediated LTR activation. Therefore, this PKC-inhibited LTR activation started in both cell types after depletion of the relevant PKCs by their downregulation. In view of these variable activating mechanisms we assume that there might be additional undiscovered yet modes of HTLV-1 LTR activation which vary in different cell types. Moreover, in line with this presumption we speculate that in HTLV-1 carriers the LTR of the latent provirus may also be reactivated by different mechanisms that vary between its different host T-lymphocyte subclones. Since this reactivation may initiate the ATL process, understanding of these mechanisms is essential for establishing strategies to block the possibility of reactivating the latent virus as preventive means for ATL development in carriers. |
| Databáze: | OpenAIRE |
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