title: Spatial and temporal dynamics of two alternatively spliced regulatory factors, lens epithelium-derived growth factor (ledgf/p75) and p52, in the nucleus.
abstract: Regulatory factors, lens epithelium-derived growth factor (LEDGF)/p75 and p52, are generated from a single LEDGF gene by alternative splicing. They have identical amino acid residues between positions 1-325, but 205 and 8 of the remaining residues are different in LEDGF and p52, respectively. LEDGF promotes growth and survival of many cell types. It has an antiapoptotic function and is a weak general transcriptional co-activator. p52 is a transcriptional activator and an essential splicing factor. We investigated the spatial and temporal dynamics of LEDGF/p75 and p52, each being tagged with a fluorescent protein, during the cell cycles of CHO-K1, MCDK, and NRK cells in culture. Both LEDGF/p75 and p52 were localized predominantly in the nucleus. LEDGF/p75 was distributed diffusely in the nucleoplasm in the G1-phase and attached to chromatin heterogeneously during the G2 and M-phases of cells. In contrast, p52 was localized in the nuclear periphery during the G1-phase and formed a speckle pattern at the S-phase. It formed a cylindrical pattern around the chromosomes during the M-phases of cells. LEDGF and p52 on sister chromatids migrated into daughter cells. Thus, LEDGF/p75 and p52 are localized in distinct nuclear compartments where they can activate transcription or splicing of pre-mRNAs.
authors.affiliation: Department of Anatomy, Nagoya University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: J
authors.initials: J
authors.lastname: Usukura
authors.forename: D P
authors.initials: DP
authors.lastname: Singh
authors.forename: L T
authors.initials: LT
authors.lastname: Chylack
authors.forename: T
authors.initials: T
authors.lastname: Shinohara
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D000906:Antibodies; D016466:CHO Cells; D002451:Cell Compartmentation / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics*; D002842:Chromatids / Q000502:physiology; D006224:Cricetinae; D016193:G1 Phase / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D049452:Green Fluorescent Proteins; D006133:Growth Substances / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007202:Indicators and Reagents / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000166:cytology; D008164:Luminescent Proteins / Q000235:genetics; D008938:Mitosis / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D012322:RNA Precursors / Q000502:physiology; D051381:Rats
chemical_list: D000906:Antibodies; D006133:Growth Substances; D007202:Indicators and Reagents; D036341:Intercellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D012322:RNA Precursors; C119380:lens epithelium-derived growth factor; D049452:Green Fluorescent Proteins