STANDARD_NAME NAKAYAMA_FRA2_TARGETS SYSTEMATIC_NAME M3782 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NAKAYAMA_FRA2_TARGETS NAMESPACE AFFY_HG_U133 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. PMID 18071306 GEOID GSE6379 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 CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Fig 6a FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_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 GENE_SYMBOLS TAGAP,RBM33,CREBRF,CKAP2,EIF4G3,GPRIN3,YTHDF3,F2R,SDCBPP2,DNAJB1,LGMN,SOX4,SQSTM1,SGK1,CDK2AP1,RGS2,HSPA1B,BCL6,DUSP4,CLEC2B,NR1D2,DBP,MKRN1,GPR18,TFPI,MT1H,MT2A,CHN1,CTTN,MYB,DUSP10,MT1F,MDM2,ZFAND5,LGR4,KLHL24,FBXO32,,SLC30A1,ZMAT3,SLC20A1,WIPF1,ING3,KLHDC7B,,,FBXO32,,SPSB3 FOUNDER_NAMES