ArticleCell death and differentiation2015
Ribosomal proteins L11 and L5 activate TAp73 by overcoming MDM2 inhibition.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 57 citations in OpenAlex.
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Nucleolus as a cornerstone linking proliferation and metabolism to cellular responses to stress: involvement of transcription factors MYC and p53.Frontiers in molecular biosciences · 2026Review
- hMTR4 promotes p53 protein degradation and tumor growth by accelerating rRNA processing and regulating the RPL5-MDM2 axis.Cell death and differentiation · 2025Article
- Extra-Ribosomal Roles for Ribosomal Proteins and Their Relevance to Tumour Suppression, Carcinogenesis and Cancer Progression.Cancers · 2025Review
- RPL22 links ribosome biogenesis, RNA splicing, and sensitivity to RNA polymerase I inhibition.Cell chemical biology · 2025Article
- Preclinical development of lentiviral vector gene therapy for Diamond-Blackfan anemia syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- TP53 mutations and MDM2 polymorphisms in breast and ovarian cancers: amelioration by drugs and natural compounds.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Mechanisms of ribosomopathy and phase separation-related ribosomopathy.Journal of Zhejiang University. Science. B · 2025Review
- Tripartite motif-containing protein 26 promotes colorectal cancer growth by inactivating p53.Cell death and differentiation · 2025Article
- Targeting BRIX1 via Engineered Exosomes Induces Nucleolar Stress to Suppress Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Tripartite motif-containing protein 26 promotes colorectal cancer growth by inactivating p53.Research square · 2024Article
- Deciphering the role of neddylation in tumor microenvironment modulation: common outcome of multiple signaling pathways.Biomarker research · 2024Review
- DDX24 promotes metastasis by regulating RPL5 in non-small cell lung cancer.Cancer medicine · 2022Article
- p53 at the crossroad of DNA replication and ribosome biogenesis stress pathways.Cell death and differentiation · 2022Review
- Olaparib Induces RPL5/RPL11-Dependent p53 ActivationFrontiers in oncology · 2022Article
- Review
- Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus.Cells · 2021Review
- The p53 family member p73 in the regulation of cell stress response.Biology direct · 2021Review
- Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy.Signal transduction and targeted therapy · 2021Review
- Single-cell transcriptomes reveal heterogeneity of high-grade serous ovarian carcinoma.Clinical and translational medicine · 2021Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Over the past decade, a number of ribosomal proteins (RPs) have been found to have a role in activating the tumor suppressor p53 by directly binding to MDM2 and impeding its activity toward p53. Herein, we report that RPL5 and RPL11 can also enhance the transcriptional activity of a p53 homolog TAp73, but through a distinct mechanism. Interestingly, even though RPL5 and RPL11 were not shown to bind to p53, they were able to directly associate with the transactivation domain of TAp73 independently of MDM2 in response to RS. This association led to perturbation of the MDM2-TAp73 interaction, consequently preventing MDM2 from its association with TAp73 target gene promoters. Furthermore, ectopic expression of RPL5 or RPL11 markedly induced TAp73 transcriptional activity by antagonizing MDM2 suppression. Conversely, ablation of either of the RPs compromised TAp73 transcriptional activity, as evident by the reduction of p21 and Puma expression, in response to 5-fluorouracil (5-FU). Consistently, overexpression of RPL5 or RPL11 enhanced, but knockdown of either of them hampered, TAp73-mediated apoptosis. Intriguingly, simultaneous knockdown of TAp73 and either of the RPs was required for rescuing the 5-FU-triggered S-phase arrest of p53-null tumor cells. These results demonstrate a novel mechanism underlying the inhibition of tumor cell proliferation and growth by these two RPs via TAp73 activation.
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