Entry Name Transcriptional misregulation in cancer - Bos taurus (cow)
Description In tumor cells, genes encoding transcription factors (TFs) are often amplified, deleted, rearranged via chromosomal translocation and inversion, or subjected to point mutations that result in a gain- or loss-of- function. In hematopoietic cancers and solid tumors, the translocations and inversions increase or deregulate transcription of the oncogene. Recurrent chromosome translocations generate novel fusion oncoproteins, which are common in myeloid cancers and soft-tissue sarcomas. The fusion proteins have aberrant transcriptional function compared to their wild-type counterparts. These fusion transcription factors alter expression of target genes, and thereby result in a variety of altered cellular properties that contribute to the tumourigenic process.
Class Human Diseases; Cancer: overviewBRITE hierarchy
Pathway map bta05202 Transcriptional misregulation in cancer
Organism Bos taurus (cow) [GN:
bta ]
Gene 281048 CD14; monocyte differentiation antigen CD14 precursor [KO:K04391 ]
281095 CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427 ]
281239 IGF1; insulin-like growth factor I preproprotein [KO:K05459 ]
281677 CEBPA; CCAAT/enhancer-binding protein alpha [KO:K09055 ]
281993 PPARG; peroxisome proliferator-activated receptor gamma [KO:K08530 ]
282227 FCGR1A; high affinity immunoglobulin gamma Fc receptor I precursor [KO:K06498 ]
282261 IGFBP3; insulin-like growth factor-binding protein 3 precursor [KO:K10138 ]
286849 CD40; tumor necrosis factor receptor superfamily member 5 precursor [KO:K03160 ]
338319 CEBPB; CCAAT/enhancer-binding protein beta [KO:K10048 ]
353110 NGFR; tumor necrosis factor receptor superfamily member 16 precursor [KO:K02583 ]
407219 MITF; microphthalmia-associated transcription factor isoform M- [KO:K09455 ]
414345 CD86; T-lymphocyte activation antigen CD86 [KO:K05413 ]
504939 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
505463 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
505691 CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622 ]
505908 PDGFA; platelet-derived growth factor subunit A precursor [KO:K04359 ]
506967 ATF1; cyclic AMP-dependent transcription factor ATF-1 [KO:K09053 ]
510442 DOT1L; histone-lysine N-methyltransferase, H3 lysine-79 specific isoform X7 [KO:K11427 ] [EC:2.1.1.360 ]
512254 MEF2C; myocyte-specific enhancer factor 2C [KO:K04454 ]
512613 CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624 ]
512915 ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500 ]
513497 CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
513669 PTCRA; pre T-cell antigen receptor alpha precursor [KO:K06056 ]
514386 BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060 ]
515670 ASPSCR1; tether containing UBX domain for GLUT4 [KO:K15627 ]
515700 IL1R2; interleukin-1 receptor type 2 precursor [KO:K04387 ]
518504 SIN3A; paired amphipathic helix protein Sin3a [KO:K11644 ]
524303 SLC45A3; solute carrier family 45 member 3 [KO:K15379 ]
526472 LDB1; LOW QUALITY PROTEIN: LIM domain-binding protein 1 [KO:K15617 ]
528877 NR4A3; nuclear receptor subfamily 4 group A member 3 isoform X3 [KO:K08559 ]
529124 FLI1; Friend leukemia integration 1 transcription factor [KO:K09436 ]
529631 RUNX1; runt-related transcription factor 1 [KO:K08367 ]
533129 ETV4; ETS translocation variant 4 isoform X3 [KO:K15592 ]
533445 ARNT2; aryl hydrocarbon receptor nuclear translocator 2 [KO:K15589 ]
534040 SPINT1; kunitz-type protease inhibitor 1 precursor [KO:K15619 ]
534346 CEBPE; CCAAT/enhancer-binding protein epsilon [KO:K10051 ]
534401 ZBTB16; zinc finger and BTB domain-containing protein 16 [KO:K10055 ]
534661 PAX8; paired box protein Pax-8 isoform X2 [KO:K09293 ]
535183 ZEB1; zinc finger E-box-binding homeobox 1 [KO:K09299 ]
536067 TAF15; TATA-binding protein-associated factor 2N [KO:K14651 ]
536911 RUNX2; runt-related transcription factor 2 isoform X6 [KO:K09278 ]
538371 PAX5; paired box protein Pax-5 isoform X1 [KO:K09383 ]
539222 PBX3; pre-B-cell leukemia transcription factor 3 [KO:K15610 ]
539314 BIRC2; baculoviral IAP repeat-containing protein 2 isoform X2 [KO:K16060 ]
539542 HHEX; hematopoietically-expressed homeobox protein HHEX [KO:K08024 ]
540309 ELK4; ETS domain-containing protein Elk-4 [KO:K04376 ]
540488 SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676 ]
540688 PBX1; pre-B-cell leukemia transcription factor 1 [KO:K09355 ]
616115 NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580 ]
618133 SUPT3H; transcription initiation protein SPT3 homolog [KO:K11313 ]
618405 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
768207 SS18L1; calcium-responsive transactivator [KO:K15623 ]
777788 DDIT3; DNA damage-inducible transcript 3 protein [KO:K04452 ]
781067 JMJD1C; probable JmjC domain-containing histone demethylation protein 2C [KO:K11449 ] [EC:1.14.11.-]
783269 BCL11B; B-cell lymphoma/leukemia 11B isoform X1 [KO:K22046 ]
Reference Authors Alcalay M, Orleth A, Sebastiani C, Meani N, Chiaradonna F, Casciari C, Sciurpi MT, Gelmetti V, Riganelli D, Minucci S, Fagioli M, Pelicci PG
Title Common themes in the pathogenesis of acute myeloid leukemia.
Journal Reference Authors Scandura JM, Boccuni P, Cammenga J, Nimer SD
Title Transcription factor fusions in acute leukemia: variations on a theme.
Journal Reference Authors Roumier C, Fenaux P, Lafage M, Imbert M, Eclache V, Preudhomme C
Title New mechanisms of AML1 gene alteration in hematological malignancies.
Journal Reference Authors Lutterbach B, Hiebert SW
Title Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation.
Journal Reference Authors Koschmieder S, Halmos B, Levantini E, Tenen DG
Title Dysregulation of the C/EBPalpha differentiation pathway in human cancer.
Journal Reference Authors Johansen LM, Iwama A, Lodie TA, Sasaki K, Felsher DW, Golub TR, Tenen DG
Title c-Myc is a critical target for c/EBPalpha in granulopoiesis.
Journal Reference Authors Gery S, Gombart AF, Yi WS, Koeffler C, Hofmann WK, Koeffler HP
Title Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia.
Journal Reference Authors Vangala RK, Heiss-Neumann MS, Rangatia JS, Singh SM, Schoch C, Tenen DG, Hiddemann W, Behre G
Title The myeloid master regulator transcription factor PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia.
Journal Reference Authors Mueller BU, Pabst T, Osato M, Asou N, Johansen LM, Minden MD, Behre G, Hiddemann W, Ito Y, Tenen DG
Title Heterozygous PU.1 mutations are associated with acute myeloid leukemia.
Journal Reference Authors Jing Y
Title The PML-RARalpha fusion protein and targeted therapy for acute promyelocytic leukemia.
Journal Reference Authors Muller-Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S, Sargin B, Kohler G, Stelljes M, Puccetti E, Ruthardt M, deVos S, Hiebert SW, Koeffler HP, Berdel WE, Serve H
Title Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells.
Journal Reference Authors Rice KL, Hormaeche I, Doulatov S, Flatow JM, Grimwade D, Mills KI, Leiva M, Ablain J, Ambardekar C, McConnell MJ, Dick JE, Licht JD
Title Comprehensive genomic screens identify a role for PLZF-RARalpha as a positive regulator of cell proliferation via direct regulation of c-MYC.
Journal Reference Authors McWhirter JR, Neuteboom ST, Wancewicz EV, Monia BP, Downing JR, Murre C
Title Oncogenic homeodomain transcription factor E2A-Pbx1 activates a novel WNT gene in pre-B acute lymphoblastoid leukemia.
Journal Reference Authors Zelent A, Greaves M, Enver T
Title Role of the TEL-AML1 fusion gene in the molecular pathogenesis of childhood acute lymphoblastic leukaemia.
Journal Reference Authors Sawinska M, Ladon D
Title Mechanism, detection and clinical significance of the reciprocal translocation t(12;21)(p12;q22) in the children suffering from acute lymphoblastic leukaemia.
Journal Reference Authors Guenther MG, Lawton LN, Rozovskaia T, Frampton GM, Levine SS, Volkert TL, Croce CM, Nakamura T, Canaani E, Young RA
Title Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia.
Journal Reference Authors Xia ZB, Popovic R, Chen J, Theisler C, Stuart T, Santillan DA, Erfurth F, Diaz MO, Zeleznik-Le NJ
Title The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression.
Journal Reference Authors Wang QF, Wu G, Mi S, He F, Wu J, Dong J, Luo RT, Mattison R, Kaberlein JJ, Prabhakar S, Ji H, Thirman MJ
Title MLL fusion proteins preferentially regulate a subset of wild-type MLL target genes in the leukemic genome.
Journal Reference Authors Zeisig BB, Milne T, Garcia-Cuellar MP, Schreiner S, Martin ME, Fuchs U, Borkhardt A, Chanda SK, Walker J, Soden R, Hess JL, Slany RK
Title Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization.
Journal Reference Authors Riz I, Hawley TS, Johnston H, Hawley RG
Title Role of TLX1 in T-cell acute lymphoblastic leukaemia pathogenesis.
Journal Reference Authors Barth TF, Martin-Subero JI, Joos S, Menz CK, Hasel C, Mechtersheimer G, Parwaresch RM, Lichter P, Siebert R, Mooller P
Title Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma.
Journal Reference Authors Hinz M, Loser P, Mathas S, Krappmann D, Dorken B, Scheidereit C
Title Constitutive NF-kappaB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells.
Journal Reference Authors Zuzel M, Cawley JC.
Title The biology of hairy cells.
Journal Reference Authors Hurt EM, Wiestner A, Rosenwald A, Shaffer AL, Campo E, Grogan T, Bergsagel PL, Kuehl WM, Staudt LM
Title Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma.
Journal Reference Authors Martinez-Garcia E, Popovic R, Min DJ, Sweet SM, Thomas PM, Zamdborg L, Heffner A, Will C, Lamy L, Staudt LM, Levens DL, Kelleher NL, Licht JD
Title The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells.
Journal Reference Authors Brito JL, Walker B, Jenner M, Dickens NJ, Brown NJ, Ross FM, Avramidou A, Irving JA, Gonzalez D, Davies FE, Morgan GJ
Title MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells.
Journal Reference Authors Iida S, Rao PH, Ueda R, Chaganti RS, Dalla-Favera R
Title Chromosomal rearrangement of the PAX-5 locus in lymphoplasmacytic lymphoma with t(9;14)(p13;q32).
Journal Reference Authors Ohno H, Ueda C, Akasaka T
Title The t(9;14)(p13;q32) translocation in B-cell non-Hodgkin's lymphoma.
Journal Reference Authors Prensner JR, Chinnaiyan AM
Title Oncogenic gene fusions in epithelial carcinomas.
Journal Reference Authors Brenner JC, Chinnaiyan AM
Title Translocations in epithelial cancers.
Journal Reference Authors Reddi HV, McIver B, Grebe SK, Eberhardt NL
Title The paired box-8/peroxisome proliferator-activated receptor-gamma oncogene in thyroid tumorigenesis.
Journal Reference Authors Medendorp K, van Groningen JJ, Vreede L, Hetterschijt L, Brugmans L, van den Hurk WH, van Kessel AG
Title The renal cell carcinoma-associated oncogenic fusion protein PRCCTFE3 provokes p21 WAF1/CIP1-mediated cell cycle delay.
Journal Reference Authors Kumar-Sinha C, Tomlins SA, Chinnaiyan AM
Title Recurrent gene fusions in prostate cancer.
Journal Reference Authors Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM
Title An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression.
Journal Reference Authors Leshem O, Madar S, Kogan-Sakin I, Kamer I, Goldstein I, Brosh R, Cohen Y, Jacob-Hirsch J, Ehrlich M, Ben-Sasson S, Goldfinger N, Loewenthal R, Gazit E, Rotter V, Berger R
Title TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.
Journal Reference Authors Cai C, Hsieh CL, Omwancha J, Zheng Z, Chen SY, Baert JL, Shemshedini L
Title ETV1 is a novel androgen receptor-regulated gene that mediates prostate cancer cell invasion.
Journal Reference Authors Helgeson BE, Tomlins SA, Shah N, Laxman B, Cao Q, Prensner JR, Cao X, Singla N, Montie JE, Varambally S, Mehra R, Chinnaiyan AM
Title Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer.
Journal Reference Authors Westermark UK, Wilhelm M, Frenzel A, Henriksson MA
Title The MYCN oncogene and differentiation in neuroblastoma.
Journal Reference Authors Bell E, Chen L, Liu T, Marshall GM, Lunec J, Tweddle DA
Title MYCN oncoprotein targets and their therapeutic potential.
Journal Reference Authors Slack A, Chen Z, Tonelli R, Pule M, Hunt L, Pession A, Shohet JM
Title The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma.
Journal Reference Authors Ochiai H, Takenobu H, Nakagawa A, Yamaguchi Y, Kimura M, Ohira M, Okimoto Y, Fujimura Y, Koseki H, Kohno Y, Nakagawara A, Kamijo T
Title Bmi1 is a MYCN target gene that regulates tumorigenesis through repression of KIF1Bbeta and TSLC1 in neuroblastoma.
Journal Reference Authors Chen L, Iraci N, Gherardi S, Gamble LD, Wood KM, Perini G, Lunec J, Tweddle DA
Title p53 is a direct transcriptional target of MYCN in neuroblastoma.
Journal Reference Authors Beierle EA, Trujillo A, Nagaram A, Kurenova EV, Finch R, Ma X, Vella J, Cance WG, Golubovskaya VM
Title N-MYC regulates focal adhesion kinase expression in human neuroblastoma.
Journal Reference Authors Iraci N, Diolaiti D, Papa A, Porro A, Valli E, Gherardi S, Herold S, Eilers M, Bernardoni R, Della Valle G, Perini G
Title A SP1/MIZ1/MYCN repression complex recruits HDAC1 at the TRKA and p75NTR promoters and affects neuroblastoma malignancy by inhibiting the cell response to NGF.
Journal Reference Authors Dreijerink KM, Hoppener JW, Timmers HM, Lips CJ
Title Mechanisms of disease: multiple endocrine neoplasia type 1-relation to chromatin modifications and transcription regulation.
Journal Reference Authors Wu X, Hua X
Title Menin, histone h3 methyltransferases, and regulation of cell proliferation: current knowledge and perspective.
Journal Reference Authors Sakurai A, Murakami A, Sano K, Uchino S, Fukushima Y
Title Unusual clinical and pathological presentation of a neuroendocrine tumor in a patient with multiple endocrine neoplasia type 1.
Journal Reference Authors Yang Y, Hua X
Title In search of tumor suppressing functions of menin.
Journal Reference Authors Aman P
Title Fusion oncogenes in tumor development.
Journal Reference Authors Fukuma M, Okita H, Hata J, Umezawa A
Title Upregulation of Id2, an oncogenic helix-loop-helix protein, is mediated by the chimeric EWS/ets protein in Ewing sarcoma.
Journal Reference Authors Cironi L, Riggi N, Provero P, Wolf N, Suva ML, Suva D, Kindler V, Stamenkovic I
Title IGF1 is a common target gene of Ewing's sarcoma fusion proteins in mesenchymal progenitor cells.
Journal Reference Authors Riggi N, Stamenkovic I.
Title The Biology of Ewing sarcoma.
Journal Reference Authors Jedlicka P
Title Ewing Sarcoma, an enigmatic malignancy of likely progenitor cell origin, driven by transcription factor oncogenic fusions.
Journal Int J Clin Exp Pathol 3:338-47 (2010)
Reference Authors Ordonez JL, Osuna D, Herrero D, de Alava E, Madoz-Gurpide J
Title Advances in Ewing's sarcoma research: where are we now and what lies ahead?
Journal Reference Authors Jishage M, Fujino T, Yamazaki Y, Kuroda H, Nakamura T
Title Identification of target genes for EWS/ATF-1 chimeric transcription factor.
Journal Reference Authors Gerald WL, Haber DA
Title The EWS-WT1 gene fusion in desmoplastic small round cell tumor.
Journal Reference Authors Filion C, Motoi T, Olshen AB, Lae M, Emnett RJ, Gutmann DH, Perry A, Ladanyi M, Labelle Y
Title The EWSR1/NR4A3 fusion protein of extraskeletal myxoid chondrosarcoma activates the PPARG nuclear receptor gene.
Journal Reference Authors Kim S, Lee HJ, Jun HJ, Kim J
Title The hTAF II 68-TEC fusion protein functions as a strong transcriptional activator.
Journal Reference Authors Sjogren H, Meis-Kindblom J, Kindblom LG, Aman P, Stenman G
Title Fusion of the EWS-related gene TAF2N to TEC in extraskeletal myxoid chondrosarcoma.
Journal Cancer Res 59:5064-7 (1999)
Reference Authors Goransson M, Elias E, Stahlberg A, Olofsson A, Andersson C, Aman P
Title Myxoid liposarcoma FUS-DDIT3 fusion oncogene induces C/EBP beta-mediated interleukin 6 expression.
Journal Reference Authors Goransson M, Andersson MK, Forni C, Stahlberg A, Andersson C, Olofsson A, Mantovani R, Aman P
Title The myxoid liposarcoma FUS-DDIT3 fusion oncoprotein deregulates NF-kappaB target genes by interaction with NFKBIZ.
Journal Reference Authors Willems SM, Schrage YM, Bruijn IH, Szuhai K, Hogendoorn PC, Bovee JV
Title Kinome profiling of myxoid liposarcoma reveals NF-kappaB-pathway kinase activity and casein kinase II inhibition as a potential treatment option.
Journal Reference Authors Linardic CM
Title PAX3-FOXO1 fusion gene in rhabdomyosarcoma.
Journal Reference Authors Barber TD, Barber MC, Tomescu O, Barr FG, Ruben S, Friedman TB
Title Identification of target genes regulated by PAX3 and PAX3-FKHR in embryogenesis and alveolar rhabdomyosarcoma.
Journal Reference Authors Ishida M, Miyamoto M, Naitoh S, Tatsuda D, Hasegawa T, Nemoto T, Yokozeki H, Nishioka K, Matsukage A, Ohki M, Ohta T
Title The SYT-SSX fusion protein down-regulates the cell proliferation regulator COM1 in t(x;18) synovial sarcoma.
Journal Reference Authors Jun HJ, Lee J, Lim do H, Park JO, Ahn G, Seo SW, Sung KS, Lim do H, Yoo KH, Choi YL
Title Expression of MET in alveolar soft part sarcoma.
Journal Reference Authors Rivlin N, Brosh R, Oren M, Rotter V
Title Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis.
Journal Reference Authors Suzuki K, Matsubara H
Title Recent advances in p53 research and cancer treatment.
Journal Related KO pathway
