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PMID: 16365316 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 52 ·2005-12-27 ·Pages 18974-9

Peloponese JM, Haller K, Miyazato A, Jeang KT

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.

MeSH Terms
Aneuploidy Animals Cell Cycle Centrosome/chemistry,ultrastructure Chromatography Chromosomes/ultrastructure Fibroblasts/metabolism,virology Gene Products, tax/metabolism Green Fluorescent Proteins/metabolism HeLa Cells Human T-lymphotropic virus 1/metabolism Humans Immunoprecipitation Mice Nuclear Proteins/metabolism,physiology Plasmids/metabolism Protein Binding Protein Structure, Tertiary Transfection ran GTP-Binding Protein/chemistry,metabolism
Chemicals
Gene Products, tax Nuclear Proteins ran-binding protein 1 Green Fluorescent Proteins ran GTP-Binding Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Peloponese Jean-Marie
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
Miyazato Akiko
Jeang Kuan-Teh
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0506659103
Published
2005-12-27
Epub
2005-00-19
Pages
18974-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1323167
Subset
IM
Grants
Intramural NIH HHS · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1073/pnas.0506659103 PMC Full Text View journal details
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