title: Protein profile of tax-associated complexes.
abstract: Infection with human T-cell leukemia virus type 1 (HTLV-1) results in adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Tax, a 40-kDa protein, regulates viral and cellular transcription, host signal transduction, the cell cycle, and apoptosis. Tax has been shown to modulate cellular CREB and NFkappaB pathways; however, to date, its role in binding to various host cellular proteins involved in tumorigenesis has not been fully described. In this study, we describe the Tax-associated proteins and their functions in cells using several approaches. Tax eluted from a sizing column mostly at an apparent molecular mass of 1800 kDa. Following Tax immunoprecipitation, washes with high salt buffer, two-dimensional gel separation, and mass spectrometric analysis, a total of 32 proteins was identified. Many of these proteins belong to the signal transduction and cytoskeleton pathways and transcription/chromatin remodeling. A few of these proteins, including TXBP151, have been shown previously to bind to Tax. The interaction of Tax with small GTPase-cytoskeleton proteins, such as ras GAP1m, Rac1, Cdc42, RhoA, and gelsolin, indicates how Tax may regulate migration, invasion, and adhesion in T-cell cancers. Finally, the physical and functional association of Tax with the chromatin remodeling SWI/SNF complex was assessed using in vitro chromatin remodeling assays, chromatin remodeling factor BRG1 mutant cells, and RNA interference experiments. Collectively, Tax is able to bind and regulate many cellular proteins that regulate transcription and cytoskeletal related pathways, which might explain the pleiotropic effects of Tax leading to T-cell transformation and leukemia in HTLV-1-infected patients.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.
authors.forename: Kaili
authors.initials: K
authors.lastname: Wu
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Bottazzi
authors.forename: Cynthia
authors.initials: C
authors.lastname: de la Fuente
authors.forename: Longwen
authors.initials: L
authors.lastname: Deng
authors.forename: Scott D
authors.initials: SD
authors.lastname: Gitlin
authors.forename: Anil
authors.initials: A
authors.lastname: Maddukuri
authors.forename: Shabnam
authors.initials: S
authors.lastname: Dadgar
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Akos
authors.initials: A
authors.lastname: Vertes
authors.forename: Anne
authors.initials: A
authors.lastname: Pumfery
authors.forename: Fatah
authors.initials: F
authors.lastname: Kashanchi
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002460:Cell Line; D016356:Gene Products, tax / Q000737:chemistry* / Q000378:metabolism*; D015490:HTLV-I Infections; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D010449:Peptide Mapping; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014764:Viral Proteins / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D016356:Gene Products, tax; D010446:Peptide Fragments; D014764:Viral Proteins