STANDARD_NAME YANAGIHARA_ESX1_TARGETS SYSTEMATIC_NAME M1538 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/YANAGIHARA_ESX1_TARGETS NAMESPACE HUMAN_SEQ_ACCESSION DESCRIPTION_BRIEF Genes down-regulated in U2-OS Tet-On cells (osteosarcoma) after induction of ESX1 [GeneID=80712] expression. DESCRIPTION_FULL Gain-of-function mutation of the K-ras gene is one of the most common genetic changes in human tumors. In tumors carrying K-ras mutation, the presence of oncogenic K-Ras is necessary for maintenance of the transformed phenotype. ESXR1 is a human paired-like homeodomain-containing protein expressed primarily in the testis. In cells, the 65-kDa full-length ESXR1 protein is proteolytically processed into an N-terminal 45-kDa fragment containing the homeodomain, which localizes exclusively within the nucleus, and a C-terminal 20-kDa fragment consisting of a proline-rich repeat region, which is located in the cytoplasm. In this work, we demonstrated that the N-terminal ESXR1 fragment specifically recognizes the TAATNNNATTA P3 consensus sequence for the paired-like homeodomain and functions as a sequence-specific transcriptional repressor. We also showed that the N-terminal ESXR1 fragment binds to the TAATGTTATTA sequence present within the first intron of the human K-ras gene and inhibits its expression at both mRNA and protein levels. Ectopic expression of the N-terminal ESXR1 fragment in human carcinoma cells that carry mutated K-ras reduces the level of K-Ras and thereby inhibits the tumor cell proliferation. Identification of ESXR1 as a transcriptional repressor of K-ras has an important implication for the development of cancer therapy that inhibits oncogenic K-Ras expression. PMID 15897875 GEOID AUTHORS Yanagihara M,Ishikawa S,Naito M,Nakajima J,Aburatani H,Hatakeyama M CONTRIBUTOR Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 1 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AA699583,AA770596,AB015706,AB085901,AJ011597,AK001861,AK023111,AK023621,AL133386,AV693202,BC001304,BC008745,BC029545,NM_000782,NM_001343,NM_001562,NM_002076,NM_002130,NM_003238,NM_003487,NM_003557,NM_003866,NM_004815,NM_004841,NM_005637,NM_144573,T90915,W26966,Z25426,Z83800 GENE_SYMBOLS ACTR2,MARCKS,IL6ST,MCF2,BDNF-AS,SNX13,TPR,RHOBTB3,BMP5,,PCLO,CRTAP,KRAS,CYP24A1,DAB2,IL18,GNS,HMGCS1,TGFB2,TAF15,PIP5K1A,INPP4B,ARHGAP29,RASAL2,SS18,NEXN,SRSF11,CLCN4,MAP4K5,DYNC2H1 FOUNDER_NAMES