title: Nuclear accumulation of the E2F heterodimer regulated by subunit composition and alternative splicing of a nuclear localization signal.
abstract: The cellular transcription factor E2F plays a critical role in integrating cell cycle progression with the transcription apparatus by virtue of a physical interaction and control by key regulators of the cell cycle, such as pRb, cyclins and cyclin-dependent kinases. Generic E2F DNA binding activity arises when a member of two families of proteins, E2F and DP, form heterodimeric complexes, an interaction which results in co-operative transcriptional and DNA binding activity. Here, we characterise a new and hitherto unexpected mechanism of control influencing the activity of E2F which is mediated at the level of intracellular location through a dependence on heterodimer formation for nuclear translocation. Nuclear accumulation is dramatically influenced by two distinct processes: alternative splicing of a nuclear localization signal and subunit composition of the E2F heterodimer. These data define a new level of control in the E2F transcription factor whereby interplay between subunits dictates the levels of nuclear DNA binding activity.
authors.affiliation: Division of Biochemistry and Molecular Biology, University of Glasgow, UK.
authors.forename: S
authors.initials: S
authors.lastname: de la Luna
authors.forename: M J
authors.initials: MJ
authors.lastname: Burden
authors.forename: C W
authors.initials: CW
authors.lastname: Lee
authors.forename: N B
authors.initials: NB
authors.lastname: La Thangue
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D019084:Fluorescent Antibody Technique, Indirect; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000737:chemistry; D021382:Protein Sorting Signals / Q000235:genetics / Q000502:physiology; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D021382:Protein Sorting Signals; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D014157:Transcription Factors