title: Nuclear-cytoplasmic trafficking of NTF2, the nuclear import receptor for the RanGTPase, is subjected to regulation.
abstract: NTF2 is a cytosolic protein responsible for nuclear import of Ran, a small Ras-like GTPase involved in a number of critical cellular processes, including cell cycle regulation, chromatin organization during mitosis, reformation of the nuclear envelope following mitosis, and controlling the directionality of nucleocytoplasmic transport. Herein, we provide evidence for the first time that translocation of the mammalian NTF2 from the nucleus to the cytoplasm to collect Ran in the GDP form is subjected to regulation. Treatment of mammalian cells with polysorbitan monolaurate was found to inhibit nuclear export of tRNA and proteins, which are processes dependent on RanGTP in the nucleus, but not nuclear import of proteins. Inhibition of the export processes by polysorbitan monolaurate is specific and reversible, and is caused by accumulation of Ran in the cytoplasm because of a block in translocation of NTF2 to the cytoplasm. Nuclear import of Ran and the nuclear export processes are restored in polysorbitan monolaurate treated cells overproducing NTF2. Moreover, increased phosphorylation of a phospho-tyrosine protein and several phospho-threonine proteins was observed in polysorbitan monolaurate treated cells. Collectively, these findings suggest that nucleocytoplasmic translocation of NTF2 is regulated in mammalian cells, and may involve a tyrosine and/or threonine kinase-dependent signal transduction mechanism(s).
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Chafe
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Pierce
authors.forename: Dev
authors.initials: D
authors.lastname: Mangroo
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000494:pharmacology; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D049790:Nuclear Export Signals; D022022:Nuclear Pore / Q000187:drug effects / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010769:Phosphothreonine / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D011136:Polysorbates / Q000494:pharmacology; D011257:Pregnancy Proteins / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D034443:RNA Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D020931:ran GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; C038965:NUTF2 protein, human; D049790:Nuclear Export Signals; D029543:Nucleocytoplasmic Transport Proteins; D011136:Polysorbates; D011257:Pregnancy Proteins; C092317:RANGAP1 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C503618:XPOT protein, human; C485184:enhanced green fluorescent protein; D003840:Deoxycholic Acid; D010769:Phosphothreonine; D049452:Green Fluorescent Proteins; D019000:Phosphotyrosine; D012343:RNA, Transfer; D020931:ran GTP-Binding Protein; D020123:Sirolimus