title: The nuclear protein ALY binds to and modulates the activity of transcription factor E2F2.
abstract: E2F transcription factors control the expression of genes involved in a variety of essential cellular processes and consequently their activity needs to be tightly regulated. Protein-protein interactions are thought to be key modulators of E2F activity. To gain insight into the mechanisms that regulate the activity of E2F2, we searched for novel proteins that associate with this transcription factor. We show that the nuclear protein ALY (THO complex 4), originally described as a transcriptional co-activator, associates with DNA-bound E2F2 and represses its transcriptional activity. The capacity of ALY to modulate gene expression was analyzed with expression microarrays by characterizing the transcriptome of E2F2 expressing HEK293T cells in which ALY was either overexpressed or silenced. We show that ALY influences the expression of more than 400 genes, including 98 genes bearing consensus E2F motifs. Thus, ALY emerges as a novel E2F2-interacting protein and a relevant modulator of E2F-responsive gene expression.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of the Basque Country, UPV/EHU, 48940 Leioa, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Osinalde
authors.forename: Miguel
authors.initials: M
authors.lastname: Olea
authors.forename: Jone
authors.initials: J
authors.lastname: Mitxelena
authors.forename: Kerman
authors.initials: K
authors.lastname: Aloria
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Rodriguez
authors.forename: Asier
authors.initials: A
authors.lastname: Fullaondo
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Arizmendi
authors.forename: Ana M
authors.initials: AM
authors.lastname: Zubiaga
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D050703:E2F2 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010449:Peptide Mapping; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: C105242:ALYREF protein, human; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors