PMID- 25294810
OWN - NLM
STAT- MEDLINE
DCOM- 20150713
LR  - 20211203
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 5
IP  - 20
DP  - 2014 Oct 30
TI  - The nuclear import of ribosomal proteins is regulated by mTOR.
PG  - 9577-93
AB  - 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.
FAU - Kazyken, Dubek
AU  - Kazyken D
AD  - 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.
FAU - Kaz, Yelimbek
AU  - Kaz Y
AD  - 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.
FAU - Kiyan, Vladimir
AU  - Kiyan V
AD  - 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.
FAU - Zhylkibayev, Assylbek A
AU  - Zhylkibayev AA
AD  - 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.
FAU - Chen, Chien-Hung
AU  - Chen CH
AD  - Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson 
      Cancer Center, Houston, TX 77030, USA.
FAU - Agarwal, Nitin K
AU  - Agarwal NK
AD  - Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson 
      Cancer Center, Houston, TX 77030, USA.
FAU - Sarbassov, Dos D
AU  - Sarbassov dos D
AD  - 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.
LA  - eng
GR  - R01 CA133522/CA/NCI NIH HHS/United States
GR  - CA 133522/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Molecular Chaperones)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Nuclear Pore Complex Proteins)
RN  - 0 (Ribosomal Proteins)
RN  - 0 (ran-binding protein 2)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Cell Line, Tumor
MH  - Cell Nucleus/*metabolism
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - Molecular Chaperones/metabolism
MH  - Multiprotein Complexes/antagonists & inhibitors/deficiency/metabolism
MH  - Neoplasms/enzymology/*metabolism
MH  - Nuclear Pore Complex Proteins/metabolism
MH  - Ribosomal Proteins/*metabolism
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/deficiency/*metabolism
PMC - PMC4259421
COIS- Conflict of interest All authors declare no conflicts of interest.
EDAT- 2014/10/09 06:00
MHDA- 2015/07/15 06:00
PMCR- 2014/10/01
CRDT- 2014/10/09 06:00
PHST- 2014/10/09 06:00 [entrez]
PHST- 2014/10/09 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - 2473 [pii]
AID - 10.18632/oncotarget.2473 [doi]
PST - ppublish
SO  - Oncotarget. 2014 Oct 30;5(20):9577-93. doi: 10.18632/oncotarget.2473.