Anatomy of Mdm2 and Mdm4 in evolution
| Autor: | David P. Lane, Farid J. Ghadessy, Ban Xiong Tan, Cynthia R. Coffill, Yaw Sing Tan, Hoe Peng Liew, Joy S. Chua |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
p53
0301 basic medicine MDMX Protein domain Genome Mdm4 03 medical and health sciences Protein Domains Mdm2 Trichoplax evolution Gene duplication Genetics Animals Humans Amino Acid Sequence Molecular Biology Gene Zinc finger Invited Review biology Nuclear Proteins Proto-Oncogene Proteins c-mdm2 Cell Biology General Medicine biology.organism_classification Biological Evolution 030104 developmental biology Evolutionary biology Models Animal Viruses Placozoa |
| Zdroj: | Journal of Molecular Cell Biology |
| ISSN: | 1759-4685 |
| DOI: | 10.1093/jmcb/mjx002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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