title: Human T-lymphotropic virus type 1 p30 interacts with REGgamma and modulates ATM (ataxia telangiectasia mutated) to promote cell survival.
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 G(2)-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.
authors.affiliation: Center for Retrovirus Research, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Rajaneesh
authors.initials: R
authors.lastname: Anupam
authors.forename: Antara
authors.initials: A
authors.lastname: Datta
authors.forename: Matthew
authors.initials: M
authors.lastname: Kesic
authors.forename: Kari
authors.initials: K
authors.lastname: Green-Church
authors.forename: Nikolozi
authors.initials: N
authors.lastname: Shkriabai
authors.forename: Mamuka
authors.initials: M
authors.lastname: Kvaratskhelia
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lairmore
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D001324:Autoantigens / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004249:DNA Damage / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016195:G2 Phase / Q000502:physiology; D057809:HEK293 Cells; D015490:HTLV-I Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D046912:Multiprotein Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C099558:Ki antigen; D046912:Multiprotein Complexes; D025521:Tumor Suppressor Proteins; D014758:Viral Core Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex