title: TBCK influences cell proliferation, cell size and mTOR signaling pathway.
abstract: Mammalian target of rapamycin (mTOR) is a central regulator for both cell proliferation and cell growth; however, little is known about the regulation of mTOR expression at the transcriptional level. Here, we provide evidences that a conserved human protein TBCK (TBC1 domain containing kinase) is involved in the regulation of mTOR signaling pathway. Depletion of TBCK significantly inhibits cell proliferation, reduces cell size, and disrupts the organization of actin, but not microtubule. Knockdown of TBCK induces a significant decrease in the protein levels of components of mTOR complex (mTORC), and suppresses the activity of mTOR signaling, but not MAPK or PDK1/Akt pathway. Further results show that TBCK influences the expression of mTORC components at the transcriptional level. Thus, these data suggest that TBCK may play an important role in cell proliferation, cell growth and actin organization possibly by modulating mTOR pathway.
authors: Department of Cell Biology and Program in Molecular Cell Biology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Yueli
authors: Y
authors: Liu
authors: Xiaoyi
authors: X
authors: Yan
authors: Tianhua
authors: T
authors: Zhou
mesh_terms: D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048429:Cell Size; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000199:Actins; D046912:Multiprotein Complexes; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C587598:TBCK protein, human; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases
references: Structure. 2009 Jan 14;17(1):128-38
references: 19141289
references: Mol Cell. 2003 Apr;11(4):895-904
references: 12718876
references: Nat Cell Biol. 2007 Mar;9(3):316-23
references: 17277771
references: Nat Cell Biol. 2004 Nov;6(11):1122-8
references: 15467718
references: Genes Dev. 2004 Aug 15;18(16):1926-45
references: 15314020
references: J Mol Biol. 1998 Sep 11;282(1):195-208
references: 9733650
references: Nat Rev Genet. 2012 Jun;13(6):383-94
references: 22568971
references: J Cell Sci. 2002 Apr 1;115(Pt 7):1355-9
references: 11896183
references: Biochem J. 2008 Jun 1;412(2):179-90
references: 18466115
references: Curr Opin Cell Biol. 2010 Aug;22(4):461-70
references: 20466531
references: Biochem J. 2011 May 15;436(1):169-79
references: 21413931
references: FASEB J. 1995 May;9(8):576-96
references: 7768349
references: Biochem Biophys Res Commun. 2007 Sep 14;361(1):218-23
references: 17658474
references: J Biol Chem. 2010 Jun 25;285(26):20109-16
references: 20427287
references: Nature. 2006 Jul 20;442(7100):303-6
references: 16855591
references: Nature. 2007 Mar 8;446(7132):153-8
references: 17344846
references: Science. 2002 Dec 6;298(5600):1912-34
references: 12471243
references: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D68-73
references: 16381958
references: Cell. 2012 Apr 13;149(2):274-93
references: 22500797
references: Cell. 2006 Oct 6;127(1):125-37
references: 16962653
references: Am J Physiol Endocrinol Metab. 2003 Nov;285(5):E964-72
references: 12876075
references: PLoS One. 2007 Nov 21;2(11):e1217
references: 18030348
references: Nat Rev Mol Cell Biol. 2012 Jan 18;13(2):67-73
references: 22251903
references: Annu Rev Biochem. 2011;80:1001-32
references: 21548787
references: Oncogene. 2011 Aug 11;30(32):3489-501
references: 21383697
references: Genetics. 2011 Dec;189(4):1177-201
references: 22174183
references: Cancer Cell. 2011 Feb 15;19(2):232-43
references: 21316602
references: Curr Biol. 2006 Sep 19;16(18):1865-70
references: 16919458
references: J Biol Chem. 2011 Oct 21;286(42):36677-85
references: 21878637
references: Cell. 2002 Jul 26;110(2):177-89
references: 12150926
references: Cell. 2000 Oct 13;103(2):253-62
references: 11057898
references: Mol Cell. 2007 Mar 23;25(6):903-15
references: 17386266
references: Cell. 2002 Jul 26;110(2):163-75
references: 12150925
references: Trends Cell Biol. 2006 Sep;16(9):443-52
references: 16879967
references: Exp Neurol. 2012 Jan;233(1):447-56
references: 22123082
references: Physiol Rev. 2011 Jan;91(1):119-49
references: 21248164
references: Mol Cell. 2012 Aug 24;47(4):535-46
references: 22795129
references: Cancer Res. 2010 Jun 15;70(12):5184-93
references: 20501828
references: Genes Chromosomes Cancer. 2010 Apr;49(4):353-67
references: 20095038
references: Hepatology. 2012 Jun;55(6):1852-62
references: 22234835
references: Cell. 2009 May 29;137(5):873-86
references: 19446321
references: Nat Rev Mol Cell Biol. 2009 Aug;10(8):513-25
references: 19603039
references: Biochem J. 2007 Aug 1;405(3):513-22
references: 17461779
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D75-80
references: 19880380
references: EMBO Rep. 2002 Aug;3(8):741-6
references: 12151332
references: Dev Biol. 1996 Jun 15;176(2):230-42
references: 8660864
references: Carcinogenesis. 2012 Dec;33(12):2391-7
references: 22983984
references: J Urol. 2011 Mar;185(3):1118-22
references: 21255804
references: Curr Biol. 2004 Jul 27;14(14):1296-302
references: 15268862
references: Cell. 2006 Feb 10;124(3):471-84
references: 16469695
references: J Biol Chem. 2007 Jul 6;282(27):20036-44
references: 17510057
references: Genes Cells. 2006 Sep;11(9):1023-37
references: 16923123