Stathminisaubiquitous,cytosolic19-kDaprotein,whichisphosphorylatedonuptofoursitesinresponsetomanyregulatorysignalswithincells.ItsmolecularcharacterizationindicatesafunctionalorganizationincludinganN-terminalregulatorydomainthatbearsthephosphorylationsites,linkedtoaputativealpha-helicalbindingdomainpredictedtoparticipateincoiled-coil,protein-proteininteractions.InaddtiontotheproteinkinasesthatphospjhorylateStathminsuchasCaMK,MAPK,p34cdc2,PKA,afewotherproteinshavebeensuggestedtointeractwithstathmininvivo.OneofthemwasidentifiedasBiP,amemberofthehsp70heat-shockproteinfamily.Anotherisapreviouslyunidentified,putativeserine/threoninekinase,KIS,whichmightberegulatedbystathminor,morelikely,bepartofthekinasescontrollingitsphosphorylationstate.Finally,twoproteins,CC1andCC2,predictedtoformalpha-helicesparticipatingincoiled-coilinteractingstructures.Ithasbeenalsosuggestthattheactionofantimicrotubuledrugscanbeaffectedbystathmininatleasttwoways:(a)altereddrugbinding;and(b)growtharrestattheG2toMboundary.Mutantp53breastcancersexhibitinghighlevelsofstathminmayberesistanttoantimicrotubuleagents.

Contributor:KosiGramatikoff,PhD

REFERENCES:ElizabethAlli,JudyBash-Babula,Jin-MingYangandWilliamN.HaitEffectofStathminontheSensitivitytoAntimicrotubuleDrugsinHumanBreastCancerCancerResearch62,6864-6869,December1,2002ManceauV,GavetO,CurmiP,SobelA.StathmininteractionwithHSC70familyproteins.Electrophoresis.1999Feb;20(2):409-17.MaucuerA,CamonisJH,SobelA.Stathmininteractionwithaputativekinaseandcoiled-coil-formingproteindomains.ProcNatlAcadSciUSA.1995Apr11;92(8):3100-4.MaucuerA,LeCaerJP,ManceauV,SobelA.SpecificSer-ProphosphorylationbytheRNA-recognitionmotifcontainingkinaseKIS.EurJBiochem.2000Jul;267(14):4456-64.MaucuerA,OzonS,ManceauV,GavetO,LawlerS,CurmiP,SobelA.KISisaproteinkinasewithanRNArecognitionmotif.JBiolChem.1997Sep12;272(37):23151-6.PAmayedetal.TheEffectofStathminPhosphorylationonMicrotubuleAssemblyDependsonTubulinCriticalConcentration*THEJOURNALOFBIOLOGICALCHEMISTRYVol.277,No.25,IssueofJune21,pp.22718–22724,2002