title: Subcellular localization and mechanisms of nucleocytoplasmic trafficking of steroid receptor coactivator-1.
abstract: Steroid hormone receptors are ligand-stimulated transcription factors that modulate gene transcription by recruiting coregulators to gene promoters. Subcellular localization and dynamic movements of transcription factors have been shown to be one of the major means of regulating their transcriptional activity. In the present report we describe the subcellular localization and the dynamics of intracellular trafficking of steroid receptor coactivator 1 (SRC-1). After its synthesis in the cytoplasm, SRC-1 is imported into the nucleus, where it activates transcription and is subsequently exported back to the cytoplasm. In both the nucleus and cytoplasm, SRC-1 is localized in speckles. The characterization of SRC-1 nuclear localization sequence reveals that it is a classic bipartite signal localized in the N-terminal region of the protein, between amino acids 18 and 36. This sequence is highly conserved within the other members of the p160 family. Additionally, SRC-1 nuclear export is inhibited by leptomycin B. The region involved in its nuclear export is localized between amino acids 990 and 1038. It is an unusually large domain differing from the classic leucine-rich NES sequences. Thus SRC-1 nuclear export involves either an alternate type of NES or is dependent on the interaction of SRC-1 with a protein, which is exported through the crm1/exportin pathway. Overall, the intracellular trafficking of SRC-1 might be a mechanism to regulate the termination of hormone action, the interaction with other signaling pathways in the cytoplasm and its degradation.
authors.affiliation: INSERM U135, Hormones, Gènes et Reproduction, IFR Bicêtre, Laboratoire d'Hormonologie et Biologie Moléculaire, AP-HP, Hôpital Bicêtre, 78 rue du Général Leclerc, 94275-Le Kremlin-Bicêtre cedex, France.
authors.forename: Larbi
authors.initials: L
authors.lastname: Amazit
authors.forename: Youssef
authors.initials: Y
authors.lastname: Alj
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Tyagi
authors.forename: Anne
authors.initials: A
authors.lastname: Chauchereau
authors.forename: Hugues
authors.initials: H
authors.lastname: Loosfelt
authors.forename: Christophe
authors.initials: C
authors.lastname: Pichon
authors.forename: Jacques
authors.initials: J
authors.lastname: Pantel
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Foulon-Guinchard
authors.forename: Philippe
authors.initials: P
authors.lastname: Leclerc
authors.forename: Edwin
authors.initials: E
authors.lastname: Milgrom
authors.forename: Anne
authors.initials: A
authors.lastname: Guiochon-Mantel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism*; D017931:DNA Primers; D051548:Histone Acetyltransferases; D006801:Humans; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D056920:Nuclear Receptor Coactivator 1; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1