Abstract

This project is to understand the processes used by the human T cell leukemia virus type 1 (HTLV-1)for the transformation of human cells. There are several concepts on how a cell can progress from normal physiology to achieve a transformed phenotype. To characterize transformation, we have studied cellular genetic integrity, cell cycle progression and the checkpoints within a cell that guard normal cellular division. We have studied several cellular proteins whose functions are perturbed by the HTLV-1 viral oncoprotein, Tax, during the course of cellular transformation. In the 2008 - 2009 period, we have made the following scientifc findings. 1) We have characterized a new Tax1-binding protein 1 (TAX1BP1) which is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation and whose activity is abrogated by Tax1. 2) We have profiled miRNA expression in HTLV-1-transformed human T-cell lines and primary peripheral blood mononuclear cells from adult T-cell leukemia patients. We have found two microRNAs that participate in the oncogenesis of HTLV-1 infected cells. 3) We have studied how Tax activates the pro-inflammatory factor NF-kappaB and how this activation is regulated by the prolyl isomerase Pin1 protein.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001023-03
Application #
7964641
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2009
Total Cost
$1,048,979
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Tang, Sai-Wen; Chen, Chia-Yen; Klase, Zachary et al. (2013) The cellular autophagy pathway modulates human T-cell leukemia virus type 1 replication. J Virol 87:1699-707
Zhang, Quan; Jeang, Kuan-Teh (2013) Long non-coding RNAs (lncRNAs) and viral infections. Biomed Pharmacother 3:34-42
Klase, Zachary; Jeang, Kuan-Teh (2013) Reciprocal functional pseudotyping of HIV-1 and HTLV-1 viral genomes by the heterologous counterpart envelope proteins. Virology 443:106-12
Zane, Linda; Yasunaga, Junichiro; Mitagami, Yu et al. (2012) Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis. Retrovirology 9:114
Chen, Chia-Yen; Chi, Ya-Hui; Mutalif, Rafidah Abdul et al. (2012) Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies. Cell 149:565-77
Chi, Ya-Hui; Chen, Chia-Yen; Jeang, Kuan-Teh (2012) Reversal of laminopathies: the curious case of SUN1. Nucleus 3:418-21
Majone, Franca; Jeang, Kuan-Teh (2012) Unstabilized DNA breaks in HTLV-1 Tax expressing cells correlate with functional targeting of Ku80, not PKcs, XRCC4, or H2AX. Cell Biosci 2:15
Zane, Linda; Jeang, Kuan-Teh (2012) The importance of ubiquitination and sumoylation on the transforming activity of HTLV Tax-1 and Tax-2. Retrovirology 9:103
Yasunaga, Junichiro; Lin, Frank C; Lu, Xiongbin et al. (2011) Ubiquitin-specific peptidase 20 targets TRAF6 and human T cell leukemia virus type 1 tax to negatively regulate NF-kappaB signaling. J Virol 85:6212-9
Banaudha, Krishna; Kaliszewski, Michael; Korolnek, Tamara et al. (2011) MicroRNA silencing of tumor suppressor DLC-1 promotes efficient hepatitis C virus replication in primary human hepatocytes. Hepatology 53:53-61

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