STANDARD_NAME	SANCHEZ_MDM2_TARGETS
SYSTEMATIC_NAME	M3206
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SANCHEZ_MDM2_TARGETS
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes up-regulated in BJ cells (forskin fibroblasts) upon overexpression of the most abundant alternative splicing forms of MDM2 [GeneID=4193], HDM2-A and HDM2-B, off a retroviral vector.
DESCRIPTION_FULL	The HDM2 oncoprotein is a cellular inhibitor of p53 and is frequently deregulated in human cancer. However, the HDM2 gene encodes alternatively spliced variants whose functional significance is poorly understood. We had previously reported the detection of alternative HDM2 forms in Hodgkin's lymphoma (HL)-derived cell lines. Here, we have cloned several of these transcripts, including the previously described HDM2-A, -B and -C (which encode the COOH terminus of HDM2), and two novel variants (HDM2-HL1 and -HL2) containing a complete p53 interaction domain. Real-time PCR assays demonstrated that HDM2-A and -B were selectively expressed by HL cell lines and primary tumors, compared with their non-neoplastic counterparts. In transient transfection experiments, alternatively spliced HDM2 isoforms were partially or totally localized within the cytoplasm. HDM2-HL2 was able to inhibit transactivation of a p53-inducible reporter construct and induced a partial relocalization of p53 to the cytoplasm. Expression of HDM2-A and -B caused the activation of p53/p21 and induced growth arrest in primary cells, but also increased the expression levels of cyclins D1 and E. Other possible genes regulated by HDM2-A and -B were identified using cDNA microarray technology. These results imply that HDM2 isoforms may have multiple effects on cell cycle control, and provide insight into the mechanisms through which these molecules contribute to tumorigenesis.
PMID	16331255
GEOID	
AUTHORS	Sánchez-Aguilera A,García JF,Sánchez-Beato M,Piris MA
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	C10orf11,C10orf116,CCND1,CDKN1A,CLIPR-59,FCGRT,HIST2H2AA,HIST2H2BE,IGFBP6,IL13RA2,IL1RN,INHBB,RABAC1,RNF113A,TIMP1
GENE_SYMBOLS	LRMDA,ADIRF,CCND1,CDKN1A,CLIP3,FCGRT,H2AC18,H2BC21,IGFBP6,IL13RA2,IL1RN,INHBB,RABAC1,RNF113A,TIMP1
FOUNDER_NAMES