title: Spatial distribution and function of sterol regulatory element-binding protein 1a and 2 homo- and heterodimers by in vivo two-photon imaging and spectroscopy fluorescence resonance energy transfer.
abstract: Sterol regulatory element-binding proteins (SREBPs) are a subfamily of basic helix-loop-helix-leucine zipper proteins that regulate lipid metabolism. We show novel evidence of the in vivo occurrence and subnuclear spatial localization of both exogenously expressed SREBP-1a and -2 homodimers and heterodimers obtained by two-photon imaging and spectroscopy fluorescence resonance energy transfer. SREBP-1a homodimers localize diffusely in the nucleus, whereas SREBP-2 homodimers and the SREBP-1a/SREBP-2 heterodimer localize predominantly to nuclear speckles or foci, with some cells showing a diffuse pattern. We also used tethered SREBP dimers to demonstrate that both homo- and heterodimeric SREBPs activate transcription in vivo. Ultrastructural analysis revealed that the punctate foci containing SREBP-2 are electron-dense nuclear bodies, similar or identical to structures containing the promyelocyte (PML) protein. Immunofluorescence studies suggest that a dynamic interplay exists between PML, as well as another component of the PML-containing nuclear body, SUMO-1, and SREBP-2 within these nuclear structures. These findings provide new insight into the overall process of transcriptional activation mediated by the SREBP family.
authors.affiliation: University of California, Irvine, Beckman Laser Institute, 1002 Health Sciences Rd., East Irvine, CA 92612, USA.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Zoumi
authors.forename: Shrimati
authors.initials: S
authors.lastname: Datta
authors.forename: Lih-Huei L
authors.initials: LH
authors.lastname: Liaw
authors.forename: Cristen J
authors.initials: CJ
authors.lastname: Wu
authors.forename: Gopi
authors.initials: G
authors.lastname: Manthripragada
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Osborne
authors.forename: Vickie J
authors.initials: VJ
authors.lastname: Lamorte
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology*; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D050356:Lipid Metabolism; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D017785:Photons; D011401:Promoter Regions, Genetic / Q000235:genetics; D000071156:Promyelocytic Leukemia Protein; D017434:Protein Structure, Tertiary; D011973:Receptors, LDL / Q000235:genetics; D025842:SUMO-1 Protein / Q000032:analysis / Q000378:metabolism; D017384:Sequence Deletion; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011973:Receptors, LDL; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D025842:SUMO-1 Protein; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D008156:Luciferases