title: The Tax oncogene enhances ELL incorporation into p300 and P-TEFb containing protein complexes to activate transcription.
abstract: The eleven-nineteen lysine-rich leukemia protein (ELL) is a key regulator of RNA polymerase II mediated transcription. ELL facilitates RNA polymerase II transcription pause site entry and release by dynamically interacting with p300 and the positive transcription elongation factor b (P-TEFb). In this study, we investigated the role of ELL during the HTLV-1 Tax oncogene induced transactivation. We show that ectopic expression of Tax enhances ELL incorporation into p300 and P-TEFb containing transcriptional complexes and the subsequent recruitment of these complexes to target genes in vivo. Depletion of ELL abrogates Tax induced transactivation of the immediate early genes Fos, Egr2 and NF-kB, suggesting that ELL is an essential cellular cofactor of the Tax oncogene. Thus, our study identifies a novel mechanism of ELL-dependent transactivation of immediate early genes by Tax and provides the rational for further defining the genome-wide targets of Tax and ELL.
authors.affiliation: National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Temesgen D
authors.initials: TD
authors.lastname: Fufa
authors.affiliation: National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Jung S
authors.initials: JS
authors.lastname: Byun
authors.affiliation: National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Clay
authors.initials: C
authors.lastname: Wakano
authors.affiliation: National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Alfonso G
authors.initials: AG
authors.lastname: Fernandez
authors.affiliation: National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Pise-Masison
authors.affiliation: National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: gardnerk@mail.nih.gov.
authors.forename: Kevin
authors.initials: K
authors.lastname: Gardner
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050881:E1A-Associated p300 Protein / Q000235:genetics* / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D042925:Positive Transcriptional Elongation Factor B / Q000235:genetics* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D035602:Transcriptional Elongation Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C090862:ELL protein, human; D051638:Ether-A-Go-Go Potassium Channels; D016356:Gene Products, tax; C092509:KCNH6 protein, human; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D034741:RNA, Small Interfering; D035602:Transcriptional Elongation Factors; C514970:tax protein, Human T-lymphotrophic virus 1; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II
keywords: ELL; HTLV-1 Tax; P-TEFb; Transcription; p300