title: Wip1 and p53 contribute to HTLV-1 Tax-induced tumorigenesis.
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.
authors.affiliation: Molecular Virology Section, Laboratory of Molecular Microbiology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Zane
authors.forename: Junichiro
authors.initials: J
authors.lastname: Yasunaga
authors.forename: Yu
authors.initials: Y
authors.lastname: Mitagami
authors.forename: Venkat
authors.initials: V
authors.lastname: Yedavalli
authors.forename: Sai-Wen
authors.initials: SW
authors.lastname: Tang
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Chen
authors.forename: Lee
authors.initials: L
authors.lastname: Ratner
authors.forename: Xiongbin
authors.initials: X
authors.lastname: Lu
authors.forename: Kuan-Teh
authors.initials: KT
authors.lastname: Jeang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002472:Cell Transformation, Viral / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D000071636:Protein Phosphatase 2C; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016356:Gene Products, tax; D016159:Tumor Suppressor Protein p53; C514970:tax protein, Human T-lymphotrophic virus 1; C000607458:PPM1D protein, human; D010749:Phosphoprotein Phosphatases; C000607468:Ppm1d protein, mouse; D000071636:Protein Phosphatase 2C