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LSA: Hichladn TAT To COMMENTARY Viral   Interactions  With the pS3 Gene in Human Cancer: NCI Workshop May Wong; Jack Gruber" sueecct futurc ancas Tcscatch cmpna SiS , Luncct multistcp process that usually prccedcd by Biological Curcinorcnc5[5 Brancn Division Canccr Ikciccumulation IAUUAGX Aesonment Renes Etiology (DCE) Annlanal Lancct Inshtute (NCD) Aeincsdn Until  recently. (umonecnic mulalions nive been Enonsored warkshop December 1992, stujico detail thoss that actraic oncorene The Addrote Tniocatutt Wata caccr; discovcry antioncogenes. TumO gupprcSS0[ Ecncs workshop chair Wcbatcr Cavence (Ludwig Insrtutc which inactivating mnulalions elici: turrgenesis, Added Cancer Rescarch Diego Calif k - membcr orthc DCE dimcngion undcrstaddins nconiata Thc Board of , Scientilfic Counzelor The cu-chalr Cardi Teunoblasioma suscenuibility Renc (RB) prOlotypc Fnvcs (Columbia UnVcIsily Acw York) . LMO SUPpIC3O gene and bccn Ghovn QupptoY Dvid Livint on (Dana-Farber Cncer lnennn Boston transformed phenutypa [Or scveral dil-rent Cincer Thc pS} Mass.) presented OycrYICY of the functional unalusie Rene growth-contm) gene that plays kcy role the RB product and mlated protcins, Thc RB sucprcston abnutnul prolifertian umOT Prolo ypE tuOr qucprernt Important dcvclopmcnc Mutntions tbc p5} tumor qupprC SOT ecnc tccuinicr cell Croljention Functicnel Inactivation most common Eenctic utcrwons associtco with typically linked appcarance ncopjastic human cancel They OccuI nieh ircoucncy Ilmost phenolynz Dvn Cclls sevctal CatnMnn cpithclial cancem shrdicd including mare benst Cenx, mumon (C.2 brcast bladder; prostalc ~msll-ccll Jung colon, Jhtcr un?, nrostale (-5) Unlil Teceniy caneci ofich RB function (8}. Several Lines  avidencc holcver little known; Ibou( numw [unclOms sugeest that the RB gcnc Product Acts conetrain growth Although pS} originally [houahi Onco roma pehuts unconsmincd Bchc . considcred hm SupCIcSsor zenc growth characteristic of canccr cclls_ Threr DNA (umor viral nomma fon_ Wild-Lypc P53]ncgatively regulatea cell prolcins ~Surlian Yirua (SV40) larc ateen Erotth division, but somg mutant Tormi pS} galn the norini EIA human ppillomavins (HPV}  E? ability Ktmuane wivininn; perhaps brcause of ths prolein Fane thown Heda gain-of-funclion mnanunc Which helcro- niodulait growuh-suppressive Iuncicn (9-11) Thrc zy80u5 state PS} aaton 5 Anun WaMIIAn discretc domin Lemned "pockel  #hick caccer nomual pyziolorical rolc pS3 moncany WmTC [nicraction Tor tncac prolcinS IrUt [ceualiol cyck.Thc_pS3 protcin csw Fao KCC[IC Anlrscs FcuncNnA micrtily phosphorylatcd ccll cycle-dependent Daltcm cdc2 this domain cecntal maintcnanct growth kinise, rcaching naama LEe pnosphuryluuon Qunn? suppicssion Acnon Dae boncs mitosia (6}. Thc pS}  prolein rcpula c ccllgrowth ccllulr Proteins. ruch E2F trinscnplo ncior regulating the Initiation DNA replication ucting (12.13). ifa oncontoicins strucnral mimics (Tn acuvator [rnscrintion (ditecdy indirecily). cither thesc ccllular prolcins thercby prcempting intcraction aumujalion Jrowtn inhioitor Rcnes rccicssion nntin| celular mariner nrescntatinn growth stimulatory Fenes PSJ has becn Impuciteo Livingston Jcrbc funcllons conit qucnCC' playing procrmmed cell death. "poptosis (7 Toce different DNA Iant Canur Tei Tmg adcnovinus papillomavirus) produce ancokene products 'Corratennd-ner Weo aenlotc C7inorenesic targct P53 chnunalc ecuyiy tranachoLOr laclor Buznch plcilinn Lincer Euclory, NCI 540 FPY  Arlnoids UD Inlunle (ransiommation 20892. rcric Jegers rcccnt javaces Tcrcarcp -Noter uection Iollot-J0t eltent 2501720221 UDunTTA Naliond Cinccr Institulc Fchnar COHMEFTART