TheLIMprotein RBTN2andthebasic helix-loop-helix protein TALlarepresent inacomplex inerythroid cells

Chromosomal translocations inT-cell acute leukemias canactivate genes encoding putative transcription factors suchastheLIMproteins RBTN1andRBTN2andthe DNA-binding basic helix-oop-helix transcription factor TALl associated withT-cell acute lymphocytic leukemia. Whilenot expressed innormal Tcells, RBTN2andTALlarecoexpressed inerythroid cells andarebothimportant forerythroid differ- entiation. Wedemonstrate, using anti-RBTN2 andanti-TALl antisera, that theLIMprotein RBTN2isnotphosphorylated andiscomplexed with theTALlphosphoprotein inthenucleus oferythroid cells. A complex containing bothRETNiand TALlalso occurs inaT-cell acute leukemia cell line. Since both RBTN2andTALlarecrucial fornormal erythropolesis, these datahaveimportant implications fortranscription networks therein. Further, since bothproteins canbeinvolved inleu- kemogenesis, these dataprovide adirect link between proteins activated bychromosomal translocations inT-cell acute leu- kemia. Chromosomal translocations inT-cell acuteleukemias are diverse eventhough this disease ishomogeneous inclinical pattern andhistological characteristics. Genesactivated by these chromosomal abnormalities havebeenidentified and their protein products showntobeputative transcription factors (1,2). Thesegenes, which mayactasmaster genes (2), include thebasic helix-loop-helix (bHLH) geneTALI formerly called TCL5andSCL), activated bytranslocation t(1;14) (3-5), andRBTN1(also called TTG-l) (6-9) and RBTN2(formerly called RBTNLIandalsocalled TTG-2) (10-12), whichareactivated bydistinct t(11;14) transloca- tions andwhich causeT-cell lymphomas intransgenic mice (refs. 13and14;andR.Larson, P.Fisch, T.Larson, and T.H.R., unpublished data). RBTNJatilpiS andRBTN2at11p13 encodeproteins comprising cysteine-rich LIMmotifs (16). Ithasbeenpro- posedthattheLIM domains function inprotein-protein interaction (17) although their precise biochemical function is unknown. Preliminary structural studies ofLIMproteins haveshownthat they arezinc-binding proteins (18-22) that probably haveafinger-type ofstructure (23). While there is noevidence that LIM-only proteins candirectly bindDNA, specific DNA recognition hasbeendemonstrated forsomeof theother T-cell acuteleukemia-associated