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Human T Lymphotropic Virus Type 1 protein Tax reduces histone levels

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dc.contributor.authorBogenberger, James M., author
dc.contributor.authorLaybourn, Pau, advisor
dc.date.accessioned2024-03-13T18:50:52Z
dc.date.available2024-03-13T18:50:52Z
dc.date.issued2008
dc.description.abstractHuman T Lymphotropic Virus Type 1 (HTLV-1) is an oncogenic retrovirus that causes adult T-cell leukemia/lymphoma (ATLL). The virally encoded Tax protein is thought to be necessary and sufficient for T-cell leukemogenesis. Tax promotes cell proliferation, represses multiple DNA repair mechanisms, deregulates cell cycle checkpoints, inhibits apoptosis and induces genomic instability. All of these effects of Tax are thought to cooperate in the development of ATLL. In this study, we demonstrate that histone protein levels are reduced in HTLV-1 infected T-cell lines as compared to uninfected T-cell lines, while the relative amount of DNA per haploid complement is unaffected. In addition, we show that replication-dependent histone transcript levels are reduced in HTLV-1 infected T-cell lines, relative to uninfected T-cell lines. Furthermore, we show that Tax expression is sufficient for reduction of replication-dependent histone transcript levels. These results demonstrate that Tax disrupts the proper regulation of replication-dependent histone gene expression. Further, our findings suggest that HTLV-1 infection uncouples replication-dependent histone gene expression and DNA replication, allowing the depletion of histone proteins with cell division. Histone proteins are involved in the regulation of all metabolic processes involving DNA including transcription, replication, repair and recombination. This study provides a previously unidentified mechanism by which Tax may directly induce chromosomal instability and deregulate gene expression through reduced histone levels.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierETDF_Bogenberger_2008_3321262.pdf
dc.identifier.urihttps://hdl.handle.net/10217/237591
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.rights.licensePer the terms of a contractual agreement, all use of this item is limited to the non-commercial use of Colorado State University and its authorized users.
dc.subjectmolecular biology
dc.subjectcellular biology
dc.subjectvirology
dc.titleHuman T Lymphotropic Virus Type 1 protein Tax reduces histone levels
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineCell and Molecular Biology
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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