ArticleNucleic acids research2003
Stimulation of human DNA polymerase epsilon by MDM2.
Article in Nucleic acids research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- Modulating the p53-MDM2 pathway: the therapeutic potential of natural compounds in cancer treatment.EXCLI journal · 2024Review
- MDM2 Implications for Potential Molecular Pathogenic Therapies of Soft-Tissue Tumors.Journal of clinical medicine · 2023Review
- TNFAIP8 modulates the survival and immune activity of Th17 cells via p53/ p21/ MDM2 pathway after acute insult.Cytokine: X · 2022Article
- Targeting Mouse Double Minute 2: Current Concepts in DNA Damage Repair and Therapeutic Approaches in Cancer.Frontiers in pharmacology · 2020Review
- The potential mechanism of extracellular high mobility group box-1 protein mediated p53 expression in immune dysfunction of T lymphocytes.Oncotarget · 2017Article
- Prediction of signaling cross-talks contributing to acquired drug resistance in breast cancer cells by Bayesian statistical modeling.BMC systems biology · 2015Article
- Identification of a new class of MDM2 inhibitor that inhibits growth of orthotopic pancreatic tumors in mice.Gastroenterology · 2014Article
- The pyrido[b]indole MDM2 inhibitor SP-141 exerts potent therapeutic effects in breast cancer models.Nature communications · 2014Article
- MDM2's social network.Oncogene · 2014Review
- The MDM2-p53 pathway revisited.Journal of biomedical research · 2013Article
- Functional analysis of Drosophila DNA polymerase ε p58 subunit.American journal of cancer research · 2013Article
- The Many Faces of MDM2 Binding Partners.Genes & cancer · 2012Article
- Therapeutic considerations for Mdm2: not just a one trick pony.Expert opinion on drug discovery · 2008Article
- MDM2 regulates dihydrofolate reductase activity through monoubiquitination.Cancer research · 2008Article
- DNA polymerase epsilon: a polymerase of unusual size (and complexity).Progress in nucleic acid research and molecular biology · 2008Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The human DNA polymerase epsilon catalytic subunit consists of a 140-kDa N-terminal domain that contains the catalytic activity and a 120-kDa C-terminal domain that binds to the other subunits and to exogenous peptides, including PCNA and MDM2. We report here that recombinant human MDM2 purified from insect cells or Escherichia coli stimulated the activity of DNA polymerase epsilon up to 10- and 40-fold, respectively, but not those of DNA polymerase beta or Klenow fragment of E.coli DNA polymerase I. Kinetic studies indicated that MDM2 increased the maximum velocity of the reaction, but did not change substrate affinities. The stimulation depended upon the interaction of the N-terminal 166 amino acid residues of MDM2 with the C-terminal domain of the full-length catalytic subunit, since the deletion of 166 amino acids from N-terminal of MDM2 or the removal of the C-terminal domain of DNA polymerase epsilon by trypsin digestion or competition for binding to it by the addition of excess C-terminal fragment eliminated the stimulation. Since DNA polymerase epsilon appears to be involved in DNA replication, recombination and repair synthesis, we suggest that MDM2 binding to DNA polymerase epsilon might be part of a reconfiguration process that allows DNA polymerase epsilon to associate with repair/recombination proteins in response to DNA damage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.