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 language | English (US) |
|---|---|
| Pages (from-to) | 7661-7668 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 286 |
| Issue number | 9 |
| DOIs | |
| State | Published - Mar 4 2011 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Human T-lymphotropic virus type 1 p30 interacts with REGγ and modulates ATM (Ataxia Telangiectasia Mutated) to promote cell survival
AU - Anupam, Rajaneesh
AU - Datta, Antara
AU - Kesic, Matthew
AU - Green-Church, Kari
AU - Shkriabai, Nikolozi
AU - Kvaratskhelia, Mamuka
AU - Lairmore, Michael Dale
PY - 2011/3/4
Y1 - 2011/3/4
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=79953171170&partnerID=8YFLogxK
U2 - 10.1074/jbc.M110.176354
DO - 10.1074/jbc.M110.176354
M3 - Article
C2 - 21216954
AN - SCOPUS:79953171170
VL - 286
SP - 7661
EP - 7668
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 9
ER -