title: The nuclear import of ribosomal proteins is regulated by mTOR.
abstract: Mechanistic target of rapamycin (mTOR) is a central component of the essential signaling pathway that regulates cell growth and proliferation by controlling anabolic processes in cells. mTOR exists in two distinct mTOR complexes known as mTORC1 and mTORC2 that reside mostly in cytoplasm. In our study, the biochemical characterization of mTOR led to discovery of its novel localization on nuclear envelope where it associates with a critical regulator of nuclear import Ran Binding Protein 2 (RanBP2). We show that association of mTOR with RanBP2 is dependent on the mTOR kinase activity that regulates the nuclear import of ribosomal proteins. The mTOR kinase inhibitors within thirty minutes caused a substantial decrease of ribosomal proteins in the nuclear but not cytoplasmic fraction. Detection of a nuclear accumulation of the GFP-tagged ribosomal protein rpL7a also indicated its dependence on the mTOR kinase activity. The nuclear abundance of ribosomal proteins was not affected by inhibition of mTOR Complex 1 (mTORC1) by rapamycin or deficiency of mTORC2, suggesting a distinctive role of the nuclear envelope mTOR complex in the nuclear import. Thus, we identified that mTOR in association with RanBP2 mediates the active nuclear import of ribosomal proteins.
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. Department of Natural Sciences, The L.N. Gumilyov Eurasian National University, Astana, 010008, Kazakhstan.
authors.forename: Dubek
authors.initials: D
authors.lastname: Kazyken
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. Department of Natural Sciences, The L.N. Gumilyov Eurasian National University, Astana, 010008, Kazakhstan.
authors.forename: Yelimbek
authors.initials: Y
authors.lastname: Kaz
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. Department of Natural Sciences, The L.N. Gumilyov Eurasian National University, Astana, 010008, Kazakhstan.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kiyan
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. Department of Natural Sciences, The L.N. Gumilyov Eurasian National University, Astana, 010008, Kazakhstan.
authors.forename: Assylbek A
authors.initials: AA
authors.lastname: Zhylkibayev
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Agarwal
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. The University of Texas Graduate School of Biomedical Sciences at Houston, TX 77030, USA.
authors.forename: Dos D
authors.initials: dos D
authors.lastname: Sarbassov
mesh_terms: D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D018832:Molecular Chaperones / Q000378:metabolism; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*
chemical_list: D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D028861:Nuclear Pore Complex Proteins; D012269:Ribosomal Proteins; C094493:ran-binding protein 2; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus