Abstract
Emerging evidence suggests that supernumerary centrosomes drive genome instability and oncogenesis. Human T-cell leukaemia virus type I (HTLV-I) is etiologically associated with adult T-cell leukaemia (ATL). ATL cells are aneuploid, but the causes of aneuploidy are incompletely understood. Here, we show that centrosome amplification is frequent in HTLV-I-transformed cells and that this phenotype is caused by the viral Tax oncoprotein. We also show that the fraction of Tax protein that localizes to centrosomes interacts with TAX1BP2, a novel centrosomal protein composed almost entirely of coiled-coil domains. Overexpression of TAX1BP2 inhibited centrosome duplication, whereas depletion of TAX1BP2 by RNAi resulted in centrosome hyperamplification. Our findings suggest that the HTLV-I Tax oncoprotein targets TAX1BP2 causing genomic instability and aneuploidy.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aneuploidy
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Animals
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CHO Cells
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COS Cells
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism*
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Centrosome / metabolism*
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Chlorocebus aethiops
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Cricetinae
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Gene Products, tax / genetics
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Gene Products, tax / metabolism*
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Genomic Instability / physiology
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HeLa Cells
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Human T-lymphotropic virus 1 / genetics
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Human T-lymphotropic virus 1 / metabolism*
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Jurkat Cells
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Leukemia-Lymphoma, Adult T-Cell / genetics
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Leukemia-Lymphoma, Adult T-Cell / metabolism*
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Membrane Proteins
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Molecular Sequence Data
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RNA Interference
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RNA, Small Interfering / physiology
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Rats
Substances
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Gene Products, tax
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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RNA, Small Interfering
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VAC14 protein, human