Human T-lymphotropic virus type 1 p30 interacts with REGγ and modulates ATM (Ataxia Telangiectasia Mutated) to promote cell survival

Rajaneesh Anupam, Antara Datta, Matthew Kesic, Kari Green-Church, Nikolozi Shkriabai, Mamuka Kvaratskhelia, Michael Dale Lairmore

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Human T-lymphotropic virus type 1 (HTLV-1) is a causative agent of adult T cell leukemia/lymphoma and a variety of inflammatory disorders. HTLV-1 encodes a nuclear localizing protein, p30, that selectively alters viral and cellular gene expression, activates G2-M cell cycle checkpoints, and is essential for viral spread. Here, we used immunoprecipitation and affinity pulldown of ectopically expressed p30 coupled with mass spectrometry to identify cellular binding partners of p30. Our data indicate that p30 specifically binds to cellular ATM (ataxia telangiectasia mutated) and REGγ (a nuclear 20 S proteasome activator). Under conditions of genotoxic stress, p30 expression was associated with reduced levels of ATM and increased cell survival. Knockdown or overexpression of REGγ paralleled p30 expression, suggesting an unexpected enhancement of p30 expression in the presence of REGγ. Finally, size exclusion chromatography revealed the presence of p30 in a high molecular mass complex along with ATM and REGγ. On the basis of our findings, we propose that HTLV-1 p30 interacts with ATM and REGγ to increase viral spread by facilitating cell survival.

Original languageEnglish (US)
Pages (from-to)7661-7668
Number of pages8
JournalJournal of Biological Chemistry
Volume286
Issue number9
DOIs
StatePublished - Mar 4 2011
Externally publishedYes

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Ataxia Telangiectasia
Human T-lymphotropic virus 1
Viruses
Cell Survival
Cells
T-cells
Size exclusion chromatography
Molecular mass
Proteasome Endopeptidase Complex
G2 Phase Cell Cycle Checkpoints
Gene expression
Adult T Cell Leukemia Lymphoma
Mass spectrometry
Viral Genes
Nuclear Proteins
Immunoprecipitation
DNA Damage
Gel Chromatography
Mass Spectrometry
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Human T-lymphotropic virus type 1 p30 interacts with REGγ and modulates ATM (Ataxia Telangiectasia Mutated) to promote cell survival. / Anupam, Rajaneesh; Datta, Antara; Kesic, Matthew; Green-Church, Kari; Shkriabai, Nikolozi; Kvaratskhelia, Mamuka; Lairmore, Michael Dale.

In: Journal of Biological Chemistry, Vol. 286, No. 9, 04.03.2011, p. 7661-7668.

Research output: Contribution to journalArticle

Anupam, Rajaneesh ; Datta, Antara ; Kesic, Matthew ; Green-Church, Kari ; Shkriabai, Nikolozi ; Kvaratskhelia, Mamuka ; Lairmore, Michael Dale. / Human T-lymphotropic virus type 1 p30 interacts with REGγ and modulates ATM (Ataxia Telangiectasia Mutated) to promote cell survival. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 9. pp. 7661-7668.
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