Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis

Linda Zane, Junichiro Yasunaga, Yu Mitagami, Venkat Yedavalli, Sai Wen Tang, Chia Yen Chen, Lee Ratner, Xiongbin Lu, Kuan Teh Jeang

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Abstract

Background: Human T-cell Leukemia Virus type 1 (HTLV-1) infects 20 million individuals world-wide and causes Adult T-cell Leukemia/Lymphoma (ATLL), a highly aggressive T-cell cancer. ATLL is refractory to treatment with conventional chemotherapy and fewer than 10% of afflicted individuals survive more than 5 years after diagnosis. HTLV-1 encodes a viral oncoprotein, Tax, that functions in transforming virus-infected T-cells into leukemic cells. All ATLL cases are believed to have reduced p53 activity although only a minority of ATLLs have genetic mutations in their p53 gene. It has been suggested that p53 function is inactivated by the Tax protein.Results: Using genetically altered mice, we report here that Tax expression does not achieve a functional equivalence of p53 inactivation as that seen with genetic mutation of p53 (i.e. a p53-/- genotype). Thus, we find statistically significant differences in tumorigenesis between Tax+p53+/+versus Tax+p53-/- mice. We also find a role contributed by the cellular Wip1 phosphatase protein in tumor formation in Tax transgenic mice. Notably, Tax+Wip1-/- mice show statistically significant reduced prevalence of tumorigenesis compared to Tax+Wip1+/+ counterparts.Conclusions: Our findings provide new insights into contributions by p53 and Wip1 in the in vivo oncogenesis of Tax-induced tumors in mice.

Original languageEnglish
Article number114
JournalRetrovirology
Volume9
DOIs
StatePublished - Dec 21 2012

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    Zane, L., Yasunaga, J., Mitagami, Y., Yedavalli, V., Tang, S. W., Chen, C. Y., Ratner, L., Lu, X., & Jeang, K. T. (2012). Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis. Retrovirology, 9, [114]. https://doi.org/10.1186/1742-4690-9-114