BTG2isfoundtobeoneoftheimmediateearlygenesup-regulatedbyneuralgrowthfactor(NGF)andepidermalgrowthfactor(EGF).Itstranscriptionallevelisalsoup-regulatedbyp53,gammarADIation,adriamycinandUVtreatmentofcells.BTGseemstobeimportantforthecellcycleprogressionasBTG2ispreferentiallyexpressedinquiescentcells.Over-expressionofBTG2decreasesthegrowthofNIH3T3cellsandinducesneuronaldifferentiationandpreventionapoptosisofPC12cells.Molecularly,BTG2expressioninduceshypophosphorylationofRBandG1arrestwhichcouldberescuedbyoverexpressionofcyclinD1.BTG1andBTG2interactwithPRMT1(predominantcellulararginineN-methyltransferase)andincreasePRMT1methyltransferaseactivity.BoxCdomaininBTG1and2areresponsIBLefortheinteraction.BoxCdomainaloneactsasadominantnegativewhichblocksPRMT1activity.PRMT1activityisessentialforNGFinducedPC12differentiation,andblockingPRMT1byBoxCdomainofBTG1or2inducesapoptosis.Inaddition,BTG2andHoxB9interactionenhancesthetranscriptionofHoxb9.Lastly,associationofBTG2andBTG1withCaf1isalsoreportedtomodulatestranscriptionalactivityofCAF1. Contributor:Yen-LiangChen,PhD REFERENCES:Berhet,C.etal.(2002).InteractionofPRMT1withBTG/TOBproteinsincellsignalling:molecularanalysisandfunctionalaspects.GenesCells7,29-39.Cortes,U.etal.(2000).BTGgeneexpressioninthep53-dependentand-independentcellularresponsetoDNAdamage.MolCarcinog27,57-64.el-Ghissassi,F.etal.(2002).BTG2(TIS21/PC3)inducesneuronaldifferentiationandpreventsapoptosisofterminallydifferentiatedPC12cells.Oncogene21,6772-6778.Guardavaccaro,D.etal.(2000).ArrestofG(1)-Sprogressionbythep53-induciblegenePC3isRbdependentandreliesontheinhibitionofcyclinD1transcription.MolCellBiol20,1797-1815.Matsuda,S.etal.(2001).InsearchofafunctionfortheTIS21/PC3/BTG1/TOBfamily.FEBSLett497,67-72.Morel,A.P.etal.(2003).BTG2antiproliferativeproteininteractswiththehumanCCR4complexexistinginvivointhreecell-cycle-regulatedforms.JCellSci116,2929-2936.Prevot,D.etal.(2000).Theleukemia-associatedproteinBtg1andthep53-regulatedproteinBtg2interactwiththehomeoproteinHoxb9andenhanceitstranscriptionalactivation.JBiolChem275,147-153.