title: Nucleolar localization of GLTSCR2/PICT-1 is mediated by multiple unique nucleolar localization sequences.
abstract: The human glioma tumor suppressor candidate region 2 gene product, GLTSCR2, also called 'protein interacting with carboxyl terminus 1' (PICT-1), has been implicated in the regulation of two major tumor suppressor proteins, PTEN and p53, and reported to bind the membrane-cytoskeleton regulator of cell signaling, Merlin. PICT-1 is a nucleolar protein, conserved among eukaryotes, and its yeast homolog has been functionally associated with ribosomal RNA processing. By means of confocal microscopy of EGFP and myc-tagged PICT-1 fusion proteins, we delineate that the nucleolar localization of PICT-1 is mediated by two independent nucleolar localization sequences (NoLS). Unlike most NoLSs, these NoLSs are relatively long with flexible boundaries and contain arginine and leucine clusters. In addition, we show that PICT-1 exhibits a nucleolar distribution similar to proteins involved in ribosomal RNA processing, yet does not colocalize precisely with either UBF1 or Fibrillarin under normal or stressed conditions. Identification of the precise location of PICT-1 and the signals that mediate its nucleolar localization is an important step towards advancing our understanding of the demonstrated influence of this protein on cell fate and tumorigenesis.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat-Gan, Israel.
authors.forename: Inna
authors.initials: I
authors.lastname: Kalt
authors.forename: Ayelet
authors.initials: A
authors.lastname: Levy
authors.forename: Tatyana
authors.initials: T
authors.lastname: Borodianskiy-Shteinberg
authors.forename: Ronit
authors.initials: R
authors.lastname: Sarid
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000235:genetics / Q000502:physiology*; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020539:Sequence Analysis, Protein; D013312:Stress, Physiological / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C500712:NOP53 protein, human; D019913:Nuclear Localization Signals; D035463:Pol1 Transcription Initiation Complex Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C485184:enhanced green fluorescent protein; C047458:fibrillarin; C063844:transcription factor UBF; D049452:Green Fluorescent Proteins