| Autor: |
Pumfery Anne, Rufner Robyn, Baylor Shanese, Maddukuri Anil, Wu Kaili, Strouss Katharine, de la Fuente Cynthia, Deng Longwen, Kehn Kylene, Bottazzi Maria Elena, Kashanchi Fatah |
| Jazyk: |
angličtina |
| Rok vydání: |
2004 |
| Předmět: |
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| Zdroj: |
Retrovirology, Vol 1, Iss 1, p 6 (2004) |
| Druh dokumentu: |
article |
| ISSN: |
1742-4690 |
| DOI: |
10.1186/1742-4690-1-6 |
| Popis: |
Abstract Background The human T-cell leukemia virus type 1 (HTLV-1) Tax protein indirectly influences transcriptional activation, signal transduction, cell cycle control, and apoptosis. The function of Tax primarily relies on protein-protein interactions. We have previously shown that Tax upregulates the cell cycle checkpoint proteins p21/waf1 and cyclin D2. Here we describe the consequences of upregulating these G1/S checkpoint regulators in HTLV-1 infected cells. Results To further decipher any physical and functional interactions between cyclin D2 and p21/waf1, we used a series of biochemical assays from HTLV-1 infected and uninfected cells. Immunoprecipitations from HTLV-1 infected cells showed p21/waf1 in a stable complex with cyclin D2/cdk4. This complex is active as it phosphorylates the Rb protein in kinase assays. Confocal fluorescent microscopy indicated that p21/waf1 and cyclin D2 colocalize in HTLV-1 infected, but not in uninfected cells. Furthermore, in vitro kinase assays using purified proteins demonstrated that the addition of p21/waf1 to cyclin D2/cdk4 increased the kinase activity of cdk4. Conclusion These data suggest that the p21/cyclin D2/cdk4 complex is not an inhibitory complex and that p21/waf1 could potentially function as an assembly factor for the cyclin D2/cdk4 complex in HTLV-1 infected cells. A by-product of this assembly with cyclin D2/cdk4 is the sequestration of p21/waf1 away from the cyclin E/cdk2 complex, allowing this active cyclin-cdk complex to phosphorylate Rb pocket proteins efficiently and push cells through the G1/S checkpoint. These two distinct functional and physical activities of p21/waf1 suggest that RNA tumor viruses manipulate the G1/S checkpoint by deregulating cyclin and cdk complexes. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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