HTLV Tax: a fascinating multifunctional co-regulator of viral and cellular pathways
Human T cell lymphotropic virus type 1 (HTLV-1) has been identified as the causative agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus infects between 15 and 20 million people worldwide of which approximately 2 to 5% develop ATL....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2012.00406/full |
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| author | Robert eCurrer Rachel eVan Duyne Rachel eVan Duyne Elizabeth eJaworski Irene eGuendel Gavin eSampey Ravi eDas Aarthi eNarayanan Fatah eKashanchi |
| author_facet | Robert eCurrer Rachel eVan Duyne Rachel eVan Duyne Elizabeth eJaworski Irene eGuendel Gavin eSampey Ravi eDas Aarthi eNarayanan Fatah eKashanchi |
| author_sort | Robert eCurrer |
| collection | DOAJ |
| description | Human T cell lymphotropic virus type 1 (HTLV-1) has been identified as the causative agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus infects between 15 and 20 million people worldwide of which approximately 2 to 5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, including the molecular characterization of Tax, the viral transactivator and oncoprotein. In spite of these efforts, the mechanisms of oncogenesis of this pleiotropic protein remain to be fully elucidated. In this review, we illustrate the multiple oncogenic roles of Tax by summarizing a recent body of literature that refines our understanding of cellular transformation. A focused range of topics are discussed in this review including Tax-mediated regulation of the viral promoter and other cellular pathways, particularly the connection of the NF-κB pathway to both post-translational modifications of Tax and sub-cellular localization. Specifically, recent research on polyubiquitination of Tax as it relates to the activation of the IkappaB kinase (IKK) complex is highlighted. Regulation of the cell cycle and DNA damage responses due to Tax are also discussed, including Tax interaction with minichromosome maintenance proteins and the role of Tax in chromatin remodeling. The recent identification of HTLV-3 has amplified the importance of the characterization of emerging viral pathogens. The challenge of the molecular determination of pathogenicity and malignant disease of this virus lies in the comparison of the viral transactivators of HTLV-1, -2, and -3 in terms of transformation and immortalization. Consequently, differences between the three proteins are currently being studied to determine what factors are required for the differences in tumorogenesis. |
| first_indexed | 2024-12-14T00:53:27Z |
| format | Article |
| id | doaj.art-0303b601355e407a87bdf65cc5424371 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-14T00:53:27Z |
| publishDate | 2012-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-0303b601355e407a87bdf65cc54243712022-12-21T23:23:42ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2012-11-01310.3389/fmicb.2012.0040631352HTLV Tax: a fascinating multifunctional co-regulator of viral and cellular pathwaysRobert eCurrer0Rachel eVan Duyne1Rachel eVan Duyne2Elizabeth eJaworski3Irene eGuendel4Gavin eSampey5Ravi eDas6Aarthi eNarayanan7Fatah eKashanchi8George Mason UniversityGeorge Mason UniversityThe George Washington UniversityGeorge Mason UniversityGeorge Mason UniversityGeorge Mason UniversityGeorge Mason UniversityGeorge Mason UniversityGeorge Mason UniversityHuman T cell lymphotropic virus type 1 (HTLV-1) has been identified as the causative agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus infects between 15 and 20 million people worldwide of which approximately 2 to 5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, including the molecular characterization of Tax, the viral transactivator and oncoprotein. In spite of these efforts, the mechanisms of oncogenesis of this pleiotropic protein remain to be fully elucidated. In this review, we illustrate the multiple oncogenic roles of Tax by summarizing a recent body of literature that refines our understanding of cellular transformation. A focused range of topics are discussed in this review including Tax-mediated regulation of the viral promoter and other cellular pathways, particularly the connection of the NF-κB pathway to both post-translational modifications of Tax and sub-cellular localization. Specifically, recent research on polyubiquitination of Tax as it relates to the activation of the IkappaB kinase (IKK) complex is highlighted. Regulation of the cell cycle and DNA damage responses due to Tax are also discussed, including Tax interaction with minichromosome maintenance proteins and the role of Tax in chromatin remodeling. The recent identification of HTLV-3 has amplified the importance of the characterization of emerging viral pathogens. The challenge of the molecular determination of pathogenicity and malignant disease of this virus lies in the comparison of the viral transactivators of HTLV-1, -2, and -3 in terms of transformation and immortalization. Consequently, differences between the three proteins are currently being studied to determine what factors are required for the differences in tumorogenesis.http://journal.frontiersin.org/Journal/10.3389/fmicb.2012.00406/fullHTLV-1NF-κBtaxoncogenesispost-translational modification |
| spellingShingle | Robert eCurrer Rachel eVan Duyne Rachel eVan Duyne Elizabeth eJaworski Irene eGuendel Gavin eSampey Ravi eDas Aarthi eNarayanan Fatah eKashanchi HTLV Tax: a fascinating multifunctional co-regulator of viral and cellular pathways Frontiers in Microbiology HTLV-1 NF-κB tax oncogenesis post-translational modification |
| title | HTLV Tax: a fascinating multifunctional co-regulator of viral and cellular pathways |
| title_full | HTLV Tax: a fascinating multifunctional co-regulator of viral and cellular pathways |
| title_fullStr | HTLV Tax: a fascinating multifunctional co-regulator of viral and cellular pathways |
| title_full_unstemmed | HTLV Tax: a fascinating multifunctional co-regulator of viral and cellular pathways |
| title_short | HTLV Tax: a fascinating multifunctional co-regulator of viral and cellular pathways |
| title_sort | htlv tax a fascinating multifunctional co regulator of viral and cellular pathways |
| topic | HTLV-1 NF-κB tax oncogenesis post-translational modification |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2012.00406/full |
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