Abnormal centrosome amplification in cells through the targeting of Ran-binding protein-1 by the human T cell leukemia virus type-1 Tax oncoprotein.
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.
Peloponese
Jean-Marie
JM
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA.
Haller
Kerstin
K
Miyazato
Akiko
A
Jeang
Kuan-Teh
KT
D000782:Aneuploidy; D000818:Animals; D002453:Cell Cycle; D018385:Centrosome / Q000737:chemistry / Q000648:ultrastructure*; D002845:Chromatography; D002875:Chromosomes / Q000648:ultrastructure*; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D016356:Gene Products, tax / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014162:Transfection; D020931:ran GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism
D016356:Gene Products, tax; D009687:Nuclear Proteins; C091775:ran-binding protein 1; D049452:Green Fluorescent Proteins; D020931:ran GTP-Binding Protein