title: Identification of FUSE-binding protein 1 as a regulatory mRNA-binding protein that represses nucleophosmin translation.
abstract: Nucleophosmin (NPM/B23) is a multifunctional oncoprotein whose protein expression levels dictate cellular growth and proliferation rates. NPM is translationally responsive to hyperactive mammalian target of rapamycin (mTOR) signals, but the mechanism of this regulation is not understood. Using chimeric translational reporters, we found that the 3' untranslated region (UTR) of the NPM messenger (m)RNA is sufficient to mediate its translational modulation by mTOR signalling. We show that far upstream element (FUSE)-binding protein 1 (FBP1) interacts specifically with the 3' UTR of NPM to repress translation. Overexpression of FBP1 resulted in translational repression of NPM mRNAs, whereas depletion of FBP1 caused a dramatic increase in NPM translation and resulted in enhanced overall cell proliferation. Thus, we propose that FBP1 is a key regulator of cell growth and proliferation through its ability to selectively bind the NPM 3' UTR and repress NPM translation.
authors.affiliation: BRIGHT Institute, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Olanich
authors.forename: B L
authors.initials: BL
authors.lastname: Moss
authors.forename: D
authors.initials: D
authors.lastname: Piwnica-Worms
authors.forename: R R
authors.initials: RR
authors.lastname: Townsend
authors.forename: J D
authors.initials: JD
authors.lastname: Weber
mesh_terms: D020121:5' Untranslated Regions; D048708:Cell Growth Processes / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000090243:Nucleophosmin; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D020123:Sirolimus / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000090243:Nucleophosmin; D004265:DNA Helicases; D020123:Sirolimus
references.citation: Cell Mol Life Sci. 2001 Feb;58(2):266-77
references.pmid: 11289308
references.citation: EMBO J. 1997 Jun 16;16(12):3693-704
references.pmid: 9218810
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13571-6
references.pmid: 12271141
references.citation: Cell. 2000 Sep 29;103(1):127-40
references.pmid: 11051553
references.citation: Histol Histopathol. 2007 Aug;22(8):895-903
references.pmid: 17503347
references.citation: Nat Cell Biol. 2002 Jul;4(7):529-33
references.pmid: 12080348
references.citation: Cell. 2006 Feb 10;124(3):471-84
references.pmid: 16469695
references.citation: Arch Biochem Biophys. 2007 Mar 1;459(1):10-9
references.pmid: 17288985
references.citation: Anal Chem. 2006 Apr 1;78(7):2171-81
references.pmid: 16579595
references.citation: Mol Cell Biol. 2006 May;26(10):3798-809
references.pmid: 16648475
references.citation: Mol Biol Cell. 2002 Jun;13(6):2016-30
references.pmid: 12058066
references.citation: Mol Cell Biol. 2004 Feb;24(3):985-96
references.pmid: 14729947
references.citation: Mol Cell Biol. 2004 Nov;24(21):9327-38
references.pmid: 15485902
references.citation: FEBS Lett. 2001 Oct 12;506(3):272-6
references.pmid: 11602260
references.citation: Nat Rev Mol Cell Biol. 2004 Oct;5(10):827-35
references.pmid: 15459663
references.citation: Genes Dev. 1994 Feb 15;8(4):465-80
references.pmid: 8125259
references.citation: Mol Cell Biol. 2009 Feb;29(3):640-9
references.pmid: 19047368
references.citation: Mol Cell. 2005 Dec 22;20(6):891-903
references.pmid: 16364914
references.citation: Biochemistry. 2004 Jun 1;43(21):6734-44
references.pmid: 15157107
references.citation: Mol Cell Biol. 2006 Sep;26(17):6584-97
references.pmid: 16914741
references.citation: Mol Cell. 2003 Nov;12(5):1151-64
references.pmid: 14636574
references.citation: Nat Rev Cancer. 2006 Jul;6(7):493-505
references.pmid: 16794633
references.citation: Biochem Soc Trans. 2002 Nov;30(Pt 6):952-8
references.pmid: 12440953
references.citation: Mol Cell. 2003 Nov;12(5):1201-11
references.pmid: 14636578
references.citation: Cancer Res. 2007 Feb 15;67(4):1609-17
references.pmid: 17308101
references.citation: J Lipid Res. 2009 May;50(5):820-31
references.pmid: 19141871
references.citation: Biochem J. 2007 Apr 15;403(2):217-34
references.pmid: 17376031
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8354-9
references.pmid: 12821781
references.citation: Mol Cell. 2004 Jun 4;14(5):571-83
references.pmid: 15175153
references.citation: Development. 2002 Dec;129(24):5609-19
references.pmid: 12421702
references.citation: Genes Dev. 1997 Apr 15;11(8):1023-36
references.pmid: 9136930
references.citation: Cancer Res. 2008 Feb 15;68(4):1046-54
references.pmid: 18281479
references.citation: Mol Cell Biol. 2000 Aug;20(15):5516-28
references.pmid: 10891491
references.citation: J Biol Chem. 2008 Sep 12;283(37):25606-25616
references.pmid: 18640985
references.citation: Nature. 2005 Sep 1;437(7055):147-53
references.pmid: 16007073
references.citation: Trends Genet. 2002 Mar;18(3):150-7
references.pmid: 11858839
references.citation: Mol Cell Biol. 2008 Dec;28(23):7050-65
references.pmid: 18809582
references.citation: Cell Mol Life Sci. 2009 Apr;66(7):1239-56
references.pmid: 19099192
references.citation: EMBO J. 2000 Mar 1;19(5):1034-44
references.pmid: 10698944
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11477-81
references.pmid: 7972087
references.citation: J Cell Sci. 2002 Dec 1;115(Pt 23):4661-9
references.pmid: 12415010
references.citation: Mol Cell Biol. 2006 Mar;26(6):2419-29
references.pmid: 16508016
references.citation: Oncogene. 2009 Sep 10;28(36):3209-20
references.pmid: 19561638
references.citation: Eur J Biochem. 2000 Nov;267(21):6321-30
references.pmid: 11029573
references.citation: Oncogene. 2008 Jul 10;27(30):4210-20
references.pmid: 18345031
references.citation: Cell. 2005 Oct 7;123(1):49-63
references.pmid: 16213212
references.citation: Mol Cell Biol. 2008 Jan;28(1):93-107
references.pmid: 17967866
references.citation: Nat Methods. 2005 Aug;2(8):607-14
references.pmid: 16094386
references.citation: Nat Rev Mol Cell Biol. 2010 Feb;11(2):113-27
references.pmid: 20094052
references.citation: Biochem Soc Trans. 2009 Feb;37(Pt 1):227-31
references.pmid: 19143637
references.citation: Mol Cell Biol. 1996 Jun;16(6):2857-64
references.pmid: 8649395
references.citation: Semin Cell Dev Biol. 2005 Feb;16(1):49-58
references.pmid: 15659339
references.citation: Nucleic Acids Res. 1997 Mar 15;25(6):1281-8
references.pmid: 9092640