ArticleThe Journal of biological chemistry2009
Nutlin-3 affects expression and function of retinoblastoma protein: role of retinoblastoma protein in cellular response to nutlin-3.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Patients with AML with WT TP53 but defective TP53-mediated apoptosis have a dismal survival.JCI insight · 2026Article
- PROTAC-Mediated Targeted Degradation of MDM2 Induces Tumor-Suppressive Signaling in Osteosarcoma Cells.Cells · 2026Article
- Targeting Cell Cycle Facilitates E1A-Independent Adenoviral Replication.Journal of virology · 2023Article
- FAM193A is a positive regulator of p53 activity.Cell reports · 2023Article
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- MDM2 as a Rational Target for Intervention in CDK4/6 Inhibitor Resistant, Hormone Receptor Positive Breast Cancer.Frontiers in oncology · 2021Review
- DREAM and RB cooperate to induce gene repression and cell-cycle arrest in response to p53 activation.Nucleic acids research · 2019Article
- CDK4 inhibition diminishes p53 activation by MDM2 antagonists.Cell death & disease · 2018Article
- Inhibition of MDM2 via Nutlin-3A: A Potential Therapeutic Approach for Pleural Mesotheliomas with MDM2-Induced Inactivation of Wild-Type P53.Journal of oncology · 2018Article
- Characterization and Molecular Mechanism of Peptide-Conjugated Gold Nanoparticle Inhibiting p53-HDM2 Interaction in Retinoblastoma.Molecular therapy. Nucleic acids · 2017Article
- p53 controls expression of the DNA deaminase APOBEC3B to limit its potential mutagenic activity in cancer cells.Nucleic acids research · 2017Article
- Combined targeting of MDM2 and CDK4 is synergistic in dedifferentiated liposarcomas.Journal of hematology & oncology · 2017Article
- The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression.Cold Spring Harbor perspectives in medicine · 2016Review
- Roles of pRB in the Regulation of Nucleosome and Chromatin Structures.BioMed research international · 2016Review
- Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle cell differentiation.Biochemical and biophysical research communications · 2015Article
- Rapamycin inhibits IGF-1-mediated up-regulation of MDM2 and sensitizes cancer cells to chemotherapy.PloS one · 2013Article
- Constitutional Nephrin Deficiency in Conditionally Immortalized Human Podocytes Induced Epithelial-Mesenchymal Transition, Supported by β-Catenin/NF-kappa B Activation: A Consequence of Cell Junction Impairment?International journal of nephrology · 2013Article
- Oncogenic functions of hMDMX in in vitro transformation of primary human fibroblasts and embryonic retinoblasts.Molecular cancer · 2011Article
- C1 Domain-targeted isophthalate derivatives induce cell elongation and cell cycle arrest in HeLa cells.PloS one · 2011Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The retinoblastoma protein (Rb) plays a pivotal role in regulating cell proliferation and apoptosis. Nutlin-3, a small molecule MDM2 antagonist blocking interaction between MDM2 and p53, activates p53 resulting in cell growth arrest or apoptosis in various cancer cells. However, the molecular basis for the different cellular responses upon nutlin-3 treatment is not fully understood. In this study, we show that nutlin-3 activates p53 resulting in a dramatic increase in MDM2 expression and a marked reduction in total Rb protein levels. Interestingly, nutlin-3 reduces the levels of hypophosphorylated Rb and induces massive apoptosis in SJSA-1 cells, which can be largely rescued by knockdown of MDM2 or by expression of constitutively active Rb. By contrast, nutlin-3 treatment of several human cancer cells, including A549, U2-OS, and HCT116, results in an accumulation of hypophosphorylated Rb and cell cycle arrest but not apoptosis. Furthermore, we show that down-regulation of Rb by nutlin-3 does not lead to E2F1 activation nor does E2F1 play a critical role for nutlin-3-induced apoptosis in SJSA-1 cells. Taken together, these results suggest that Rb plays a critical role in influencing cellular response to activation of p53 pathway by nutlin-3.
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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.