Abnormal centrosome amplification in cells through the targeting of Ran-binding protein-1 by the human T cell leukemia virus type-1 Tax oncoprotein

Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18974-9. doi: 10.1073/pnas.0506659103. Epub 2005 Dec 19.

Abstract

Human T cell leukemia virus type-1 (HTLV-1) is an oncogenic retrovirus etiologically causal of adult T cell leukemia. The virus encodes a Tax oncoprotein that functions in transcriptional regulation, cell cycle control, and transformation. Because adult T cell leukemia like many other human cancers is a disease of genomic instability with frequent gains and losses of chromosomes, to understand this disease it is important to comprehend how HTLV-1 engenders aneuploidy in host cells. In this regard, loss of cell cycle checkpoints permits tolerance of aneuploidy but does not explain how aneuploidy is created. We show here that HTLV-1 Tax causes abnormal centrosome fragmentation in the mitotic phase of the cell cycle. We report that Tax directly binds Ran and Ran-binding protein-1, locates to centrosomes/spindle poles, and causes supernumerary centrosomes.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aneuploidy
  • Animals
  • Cell Cycle
  • Centrosome / chemistry
  • Centrosome / ultrastructure*
  • Chromatography
  • Chromosomes / ultrastructure*
  • Fibroblasts / metabolism
  • Fibroblasts / virology
  • Gene Products, tax / metabolism*
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Human T-lymphotropic virus 1 / metabolism*
  • Humans
  • Immunoprecipitation
  • Mice
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Transfection
  • ran GTP-Binding Protein / chemistry
  • ran GTP-Binding Protein / metabolism

Substances

  • Gene Products, tax
  • Nuclear Proteins
  • ran-binding protein 1
  • Green Fluorescent Proteins
  • ran GTP-Binding Protein