miR-661 downregulates both Mdm2 and Mdm4 to activate p53
نویسندگان
چکیده
منابع مشابه
Mdm2 and Mdm4 loss regulates distinct p53 activities.
Mutational inactivation of p53 is a hallmark of most human tumors. Loss of p53 function also occurs by overexpression of negative regulators such as MDM2 and MDM4. Deletion of Mdm2 or Mdm4 in mice results in p53-dependent embryo lethality due to constitutive p53 activity. However, Mdm2(-/-) and Mdm4(-/-) embryos display divergent phenotypes, suggesting that Mdm2 and Mdm4 exert distinct control ...
متن کاملHeterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability.
Mdm2 and Mdm4 are homologous RING domain-containing proteins that negatively regulate the tumor suppressor p53 under physiological and stress conditions. The RING domain of Mdm2 encodes an E3-ubiquitin ligase that promotes p53 degradation. In addition, Mdm2 and Mdm4 interact through their respective RING domains. The in vivo significance of Mdm2-Mdm4 heterodimerization in regulation of p53 func...
متن کاملMdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells in vivo.
The Mdm2 and Mdm4 oncoproteins are key negative regulators of the p53 tumor suppressor. However, their physiological contributions to the regulation of p53 stability and activity remain highly controversial. Here, we combined a p53 knock-in allele, in which p53 is silenced by a transcriptional stop element flanked by loxP sites, with the mdm2- and mdm4-null alleles. This approach allows Cre-med...
متن کاملThe p53-Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans.
The extant jawless vertebrates, represented by lampreys and hagfish, are the oldest group of vertebrates and provide an interesting genomic evolutionary pivot point between invertebrates and jawed vertebrates. Through genome analysis of one of these jawless vertebrates, the Japanese lamprey (Lethenteron japonicum), we identified all three members of the important p53 transcription factor family...
متن کاملp53 alpha-Helix mimetics antagonize p53/MDM2 interaction and activate p53.
Overexpression or hyperactivation of MDM2 contributes to functional inactivation of wild-type p53 in nearly 50% of tumors. Inhibition of p53 by MDM2 depends on binding between an NH(2)-terminal (residues 16-28) p53 alpha-helical peptide and a hydrophobic pocket on MDM2, presenting an attractive target for development of inhibitors against tumors expressing wild-type p53. Here we report that nov...
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ژورنال
عنوان ژورنال: Cell Death & Differentiation
سال: 2013
ISSN: 1350-9047,1476-5403
DOI: 10.1038/cdd.2013.146