title: Anatomy of Mdm2 and Mdm4 in evolution.
abstract: Mouse double minute (Mdm) genes span an evolutionary timeframe from the ancient eukaryotic placozoa Trichoplax adhaerens to Homo sapiens, implying a significant and possibly conserved cellular role throughout history. Maintenance of DNA integrity and response to DNA damage involve many key regulatory pathways, including precise control over the tumour suppressor protein p53. In most vertebrates, degradation of p53 through proteasomal targeting is primarily mediated by heterodimers of Mdm2 and the Mdm2-related protein Mdm4 (also known as MdmX). Both Mdm2 and Mdm4 have p53-binding regions, acidic domains, zinc fingers, and C-terminal RING domains that are conserved throughout evolution. Vertebrates typically have both Mdm2 and Mdm4 genes, while analyses of sequenced genomes of invertebrate species have identified single Mdm genes, suggesting that a duplication event occurred prior to emergence of jawless vertebrates about 550-440 million years ago. The functional relationship between Mdm and p53 in T. adhaerens, an organism that has existed for 1 billion years, implies that these two proteins have evolved together to maintain a conserved and regulated function.
authors.affiliation: p53 Laboratory, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #06-06, Singapore138648, Singapore.
authors.forename: Ban Xiong
authors.initials: BX
authors.lastname: Tan
authors.affiliation: p53 Laboratory, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #06-06, Singapore138648, Singapore.
authors.forename: Hoe Peng
authors.initials: HP
authors.lastname: Liew
authors.affiliation: p53 Laboratory, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #06-06, Singapore138648, Singapore.
authors.forename: Joy S
authors.initials: JS
authors.lastname: Chua
authors.affiliation: p53 Laboratory, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #06-06, Singapore138648, Singapore.
authors.forename: Farid J
authors.initials: FJ
authors.lastname: Ghadessy
authors.affiliation: Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), 30 Biopolis St, #07-01,Singapore138671, Singapore.
authors.forename: Yaw Sing
authors.initials: YS
authors.lastname: Tan
authors.affiliation: p53 Laboratory, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #06-06, Singapore138648, Singapore.
authors.forename: David P
authors.initials: DP
authors.lastname: Lane
authors.affiliation: p53 Laboratory, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #06-06, Singapore138648, Singapore.
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Coffill
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D006801:Humans; D023421:Models, Animal; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D000072417:Protein Domains; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry / Q000378:metabolism*; D014780:Viruses / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Mdm2; Mdm4; evolution; p53