The organization and expression of the mdm2 gene.
The mdm2 gene encodes a zinc finger protein that negatively regulates p53 function by binding and masking the p53 transcriptional activation domain. Two different promoters control expression of mdm2, one of which is also transactivated by p53. We cloned and characterized the mdm2 gene from a murine 129 library. It contained at least 12 exons and spanned approximately 25 kb of DNA. Sequencing of the mdm2 gene revealed three nucleotide differences that resulted in amino acid substitutions in the previously published mdm2 sequence. Sequencing of normal BalbC/J DNA and the original cosmid clone isolated from the 3T3DM cell line revealed that they are identical, suggesting that the published sequence is in error at these three positions. In addition, we analyzed the expression pattern of mdm2 and found ubiquitous low-level expression throughout embryo development and in adult tissues. Analysis of mRNA from numerous tissues for several mdm2 spliced variants that had been identified in the transformed 3T3DM cell line revealed that these variants could not be detected in the developing embryo or in adult tissues.
de Oca Luna
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RM
Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston, Texas, 77030, USA.
Tabor
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Eberspaecher
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Hulboy
D L
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Worth
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Colman
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Finlay
C A
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Lozano
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G
D016475:3T3 Cells; D000818:Animals; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism; D003001:Cloning, Molecular; D003360:Cosmids; D017931:DNA Primers; D004622:Embryo, Mammalian; D005091:Exons; D005727:Ganglia, Spinal / Q000196:embryology / Q000378:metabolism; D015870:Gene Expression; D015698:Genomic Library; D017403:In Situ Hybridization; D007438:Introns; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D015183:Restriction Mapping; D016335:Zinc Fingers
D016375:Antisense Elements (Genetics); D017931:DNA Primers; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2