ArticleThe FEBS journal2012
Specific domains of nucleolin interact with Hdm2 and antagonize Hdm2-mediated p53 ubiquitination.
Article in The FEBS journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Fulfilling multiple roles in PROTAC design: The emerging potential of oligonucleotides.European journal of medicinal chemistry · 2026Review
- Altered Expression of Ribosome Biogenesis Regulators (TP53, C-MYC, FBL, and NCL) in Precursor B-cell Acute Lymphoblastic Leukemia and Neuroblastoma.Current issues in molecular biology · 2026Article
- Dual functionality of MDM2 in PROTACs expands the horizons of targeted protein degradation.Biomarker research · 2025Review
- Article
- Insights Into Mitochondrial Dynamics in Chlamydial Infection.Frontiers in cellular and infection microbiology · 2022Review
- Targeting the oncogenic TBX3:nucleolin complex to treat multiple sarcoma subtypes.American journal of cancer research · 2021Article
- Nucleolin Rescues TDP-43 Toxicity in Yeast and Human Cell Models.Frontiers in cellular neuroscience · 2021Article
- The nucleolus, an ally, and an enemy of cancer cells.Histochemistry and cell biology · 2018Review
- MDM2 Degrades Deacetylated Nucleolin Through Ubiquitination to Promote Glioma Stem-Like Cell Enrichment for Chemotherapeutic Resistance.Molecular neurobiology · 2018Article
- Nucleolin phosphorylation regulates PARN deadenylase activity during cellular stress response.RNA biology · 2018Article
- Nucleolin and ErbB2 inhibition reduces tumorigenicity of ErbB2-positive breast cancer.Cell death & disease · 2018Article
- Nucleolin-binding by ErbB2 enhances tumorigenicity of ErbB2-positive breast cancer.Oncotarget · 2016Article
- C23 promotes tumorigenesis via suppressing p53 activity.Oncotarget · 2016Article
- Downregulation of miR-320a/383-sponge-like long non-coding RNA NLC1-C (narcolepsy candidate-region 1 genes) is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation.Cell death & disease · 2015Article
- Structural basis of nucleic acid binding by Nicotiana tabacum glycine-rich RNA-binding protein: implications for its RNA chaperone function.Nucleic acids research · 2014Article
- Induced expression of nucleolin phosphorylation-deficient mutant confers dominant-negative effect on cell proliferation.PloS one · 2014Article
- Nucleolin regulates phosphorylation and nuclear export of fibroblast growth factor 1 (FGF1).PloS one · 2014Article
- Regulation of p53 level by UBE4B in breast cancer.PloS one · 2014Article
- Ubiquitin at the crossroad of cell death and survival.Chinese journal of cancer · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Nucleolin is an abundant multifunctional nucleolar protein with defined roles in ribosomal RNA processing, RNA polymerase I catalyzed transcription and the regulation of apoptosis. Earlier we reported that human nucleolin binds to the p53 antagonist human double minute 2 (Hdm2) as determined by reciprocal co-immunoprecipitation assays using cell lysates. We also demonstrated that nucleolin antagonizes Hdm2-mediated degradation of p53. Here, we identify specific domains of nucleolin and Hdm2 proteins that support mutual interaction and investigate the implications of complex formation on p53 ubiquitination and protein levels. Our data indicate that the nucleolin N-terminus as well as the central RNA-binding domain (RBD) are predominantly involved in binding to Hdm2. The nucleolin RBD robustly bound to the NLS/NES (nuclear localization and export signals) domain of Hdm2 in vitro, while the N-terminus of nucleolin preferentially associated with the Hdm2 RING (really interesting new gene) domain expressed in cells. We further demonstrate that the C-terminal glycine-arginine rich domain of nucleolin serves as the predominant binding domain for direct interaction with p53. While overexpression of nucleolin or its various domains had no significant effect on Hdm2 auto-ubiquitination, the nucleolin RBD antagonized the Hdm2 E3 ligase activity against p53, leading to p53 stabilization. Conversely, the adjacent glycine-arginine rich domain of nucleolin interacted with p53 causing a modest stimulatory effect on p53 ubiquitination. These data suggest that changes in nucleolin conformation can alter the availabilities of such domains in vivo to modulate the overall impact of nucleolin on Hdm2 activity and hence on p53 stability.
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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.