PMID:25294810

Citation	Kazyken, D, Kaz, Y, Kiyan, V, Zhylkibayev, AA, Chen, CH, Agarwal, NK and Sarbassov, dos D (2014) The nuclear import of ribosomal proteins is regulated by mTOR. Oncotarget 5:9577-93
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.
Links	PubMed PMC4259421 Online version:10.18632/oncotarget.2473
Keywords	Active Transport, Cell Nucleus; Cell Line, Tumor; Cell Nucleus/metabolism; HEK293 Cells; HeLa Cells; Humans; Molecular Chaperones/metabolism; Multiprotein Complexes/antagonists & inhibitors; Multiprotein Complexes/deficiency; Multiprotein Complexes/metabolism; Neoplasms/enzymology; Neoplasms/metabolism; Nuclear Pore Complex Proteins/metabolism; Ribosomal Proteins/metabolism; Sirolimus/pharmacology; TOR Serine-Threonine Kinases/antagonists & inhibitors; TOR Serine-Threonine Kinases/deficiency; TOR Serine-Threonine Kinases/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:MTOR		GO:0005635: nuclear envelope	ECO:0000314:		C		Figure 2A shows immunostaining of mTOR in the nuclear envelope.	complete CACAO 11483
HUMAN:MTOR		GO:0005635: nuclear envelope	ECO:0000314:		C		Figure 2A shows immunostaining of mTOR in the nuclear envelope.	complete CACAO 11504
MOUSE:RBP2		GO:0005635: nuclear envelope	ECO:0000314:		C		Figure 2B shows immunostaining of RanBP2 in the nuclear envelope.	complete CACAO 11484
MOUSE:RL7A		GO:0005730: nucleolus	ECO:0000314:		C		Figure 4(C1) shows accumulation of GFP-RPL7a in nucleolus of control cells.	complete CACAO 11485
HUMAN:RBP2		GO:0005635: nuclear envelope	ECO:0000314:		C		Figure 2B shows immunostaining of RanBP2 in the nuclear envelope.	complete CACAO 11505
HUMAN:RL7A		GO:0005730: nucleolus	ECO:0000314:		C		Figure 4(C1) shows accumulation of GFP-RPL7a in nucleolus of control cells.	complete CACAO 11506

References

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