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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Hs" NAME="export">
    <GENESET STANDARD_NAME="NAKAYAMA_FRA2_TARGETS" SYSTEMATIC_NAME="M3782" HISTORICAL_NAMES="" PMID="18071306" AUTHORS="Nakayama T,Hieshima K,Arao T,Jin Z,Nagakubo D,Shirakawa AK,Yamada Y,Fujii M,Oiso N,Kawada A,Nishio K,Yoshie O" GEOID="GSE6379" EXACT_SOURCE="Fig 6a" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="" CHIP="AFFY_HG_U133" CONTRIBUTOR="Jessica Robertson" CONTRIBUTOR_ORG="MSigDB Team" DESCRIPTION_BRIEF="Genes down-regulated in ST1 cells (adult T-cell leukemia, ATL) after knockdown of FRA2 [GeneID=2355] by RNAi." DESCRIPTION_FULL="Adult T-cell leukemia (ATL) is a mature CD4+ T-cell malignancy etiologically associated with human T-cell leukemia virus type 1 (HTLV-1). Primary ATL cells frequently express CCR4 at high levels. Since HTLV-1 Tax does not induce CCR4 expression, transcription factor(s) constitutively active in ATL may be responsible for its strong expression. We identified an activator protein-1 (AP-1) site in the CCR4 promoter as the major positive regulatory element in ATL cells. Among the AP-1 family members, Fra-2, JunB and JunD are highly expressed in fresh primary ATL cells. Consistently, the Fra-2/JunB and Fra-2/JunD heterodimers strongly activated the CCR4 promoter in Jurkat cells. Furthermore, Fra-2 small interfering RNA (siRNA) or JunD siRNA, but not JunB siRNA, effectively reduced CCR4 expression and cell growth in ATL cells. Conversely, Fra-2 or JunD overexpression promoted cell growth in Jurkat cells. We identified 49 genes, including c-Myb, BCL-6 and MDM2, which were downregulated by Fra-2 siRNA in ATL cells. c-Myb, BCL-6 and MDM2 were also downregulated by JunD siRNA. As Fra-2, these proto-oncogenes were highly expressed in primary ATL cells but not in normal CD4+ T cells. Collectively, aberrantly expressed Fra-2 in association with JunD may play a major role in CCR4 expression and oncogenesis in ATL." TAGS="" MEMBERS="1552542_s_at,1554096_a_at,1554229_at,1554264_at,1554309_at,1556697_at,1564053_a_at,1569642_at,1569952_x_at,200664_s_at,201212_at,201416_at,201471_s_at,201739_at,201938_at,202388_at,202581_at,203140_at,204015_s_at,209732_at,209750_at,209782_s_at,209845_at,210279_at,210665_at,211456_x_at,212185_x_at,212624_s_at,214073_at,215152_at,215501_s_at,217165_x_at,217373_x_at,217741_s_at,218326_s_at,221985_at,225803_at,227368_at,228181_at,228315_at,230494_at,231182_at,231863_at,236285_at,239393_at,240622_at,241763_s_at,243797_at,46256_at" MEMBERS_SYMBOLIZED="BCL6,CDK2AP1,CHN1,CKAP2,CLEC2B,CREBRF,CTTN,DBP,DNAJB1,DUSP10,DUSP4,EIF4G3,F2R,FBXO32,GPR18,GPRIN3,HSPA1B,ING3,KLHDC7B,KLHL24,LGMN,LGR4,MDM2,MKRN1,MT1F,MT1H,MT2A,MYB,NR1D2,RBM33,RGS2,SDCBPP2,SGK1,SLC20A1,SLC30A1,SOX4,SPSB3,SQSTM1,STK17B,TAGAP,TFPI,WIPF1,YTHDF3,ZFAND5,ZMAT3" MEMBERS_EZID="100129960,11221,1123,113730,114907,117289,153222,155435,1628,1846,2017,2149,23608,253943,26586,2841,285513,3304,3337,4193,4494,4496,4502,4602,54556,54800,55366,5641,5997,604,64393,6446,6574,6659,7035,7456,7763,7779,8099,8672,8878,90864,9262,9975,9976" MEMBERS_MAPPING="1552542_s_at,TAGAP,117289|1554096_a_at,RBM33,155435|1554229_at,CREBRF,153222|1554264_at,CKAP2,26586|1554309_at,EIF4G3,8672|1556697_at,GPRIN3,285513|1564053_a_at,YTHDF3,253943|1569642_at,F2R,2149|1569952_x_at,SDCBPP2,100129960|200664_s_at,DNAJB1,3337|201212_at,LGMN,5641|201416_at,SOX4,6659|201471_s_at,SQSTM1,8878|201739_at,SGK1,6446|201938_at,CDK2AP1,8099|202388_at,RGS2,5997|202581_at,HSPA1B,3304|203140_at,BCL6,604|204015_s_at,DUSP4,1846|209732_at,CLEC2B,9976|209750_at,NR1D2,9975|209782_s_at,DBP,1628|209845_at,MKRN1,23608|210279_at,GPR18,2841|210665_at,TFPI,7035|211456_x_at,MT1H,4496|212185_x_at,MT2A,4502|212624_s_at,CHN1,1123|214073_at,CTTN,2017|215152_at,MYB,4602|215501_s_at,DUSP10,11221|217165_x_at,MT1F,4494|217373_x_at,MDM2,4193|217741_s_at,ZFAND5,7763|218326_s_at,LGR4,55366|221985_at,KLHL24,54800|225803_at,FBXO32,114907|227368_at,null,null|228181_at,SLC30A1,7779|228315_at,ZMAT3,64393|230494_at,SLC20A1,6574|231182_at,WIPF1,7456|231863_at,ING3,54556|236285_at,KLHDC7B,113730|239393_at,null,null|240622_at,null,null|241763_s_at,FBXO32,114907|243797_at,STK17B,9262|46256_at,SPSB3,90864" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="C2" ORGANISM="Homo sapiens" SUB_CATEGORY_CODE="CGP"/>
</MSIGDB>
