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Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Tosi, Giovanna Pilotti, Elisabetta Mortara, Lorenzo Barbaro, Andrea De Lerma Casoli, Claudio Accolla, Roberto S. |
| Copyright Year | 2006 |
| Abstract | The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from positions 64-144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300/CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells. |
| Starting Page | 2061 |
| Ending Page | 2066 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pnas.org/content/103/34/12861.full.pdf |
| PubMed reference number | 16908858v1 |
| Volume Number | 103 |
| Issue Number | 34 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Chronic Lymphocytic Leukemia DNA Replication Dual Histocompatibility Antigens Class II Human T-lymphotropic virus 2 Leukemia, B-Cell Leukemia, T-Cell Long Terminal Repeat MHC2TA protein, human Map Response Elements TRANSCRIPTION FACTOR Trans-Activation, Genetic Trans-Activators Transcription, Genetic physical hard work |
| Content Type | Text |
| Resource Type | Article |