ArticleProceedings of the National Academy of Sciences of the United States of America2003
Crystal structure of the retinoblastoma tumor suppressor protein bound to E2F and the molecular basis of its regulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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76 citing papers in PubMed, 162 citations in OpenAlex.
- Biallelic loss of RB1 in hepatocellular carcinoma as synthetic lethal target for artificial intelligence-guided therapy.Signal transduction and targeted therapy · 2026Article
- Integrative Genomic Mapping and Visualization From Curated Public Datasets Reveals Germline RB1 Variant Diversity in Retinoblastoma.Investigative ophthalmology & visual science · 2026Article
- RB1-I680T mutation potentiates tumor growth and chemotherapy sensitivity in non-small cell lung cancer via derepressing E2F1 transcription.Cell communication and signaling : CCS · 2026Article
- One hotspotFrontiers in oncology · 2026Article
- Review
- Selective Up-Regulation of Tumor Suppressor Gene Retinoblastoma by Bisacridine Derivative Through Gene Promoter Quadruplex Structures for Cancer Treatment.International journal of molecular sciences · 2025Article
- Epstein-Barr virus replication within differentiated epithelia requires pRb sequestration of activator E2F transcription factors.Journal of virology · 2024Article
- Exploring treatment options in cancer: Tumor treatment strategies.Signal transduction and targeted therapy · 2024Review
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- The Four Homeostasis Knights: In Balance upon Post-Translational Modifications.International journal of molecular sciences · 2022Review
- Emerging New Therapeutics for Retinoblastoma.Ocular oncology and pathology · 2022Review
- Structural basis for tunable affinity and specificity of LxCxE-dependent protein interactions with the retinoblastoma protein family.Structure (London, England : 1993) · 2022Article
- miRNA-10a-5p Targeting the BCL6 Gene Regulates Proliferation, Differentiation and Apoptosis of Chicken Myoblasts.International journal of molecular sciences · 2022Article
- RB1 loss triggers dependence on ESRRG in retinoblastoma.Science advances · 2022Article
- Post-translational modifications on the retinoblastoma protein.Journal of biomedical science · 2022Review
- Understanding Retinoblastoma Post-Translational Regulation for the Design of Targeted Cancer Therapies.Cancers · 2022Review
- Retinoblastoma Protein Paralogs and Tumor Suppression.Frontiers in genetics · 2022Review
- Article
- The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex.Journal of experimental & clinical cancer research : CR · 2021Article
- The Function of SUMOylation and Its Role in the Development of Cancer Cells under Stress Conditions: A Systematic Review.Stem cells international · 2020Review
16 more citing papers are in PubMed but not listed here.
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10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The retinoblastoma tumor suppressor protein (pRb) regulates the cell cycle, facilitates differentiation, and restrains apoptosis. Furthermore, dysfunctional pRb is thought to be involved in the development of most human malignancies. Many of the functions of pRb are mediated by its regulation of the E2F transcription factors. To understand the structural basis for this regulation, we have determined the crystal structure of a fragment of E2F in complex with the pocket domain of the tumor suppressor protein. The pRb pocket, comprising the A and B cyclin-like domains, is the major focus of tumourigenic mutations in the protein. The fragment of E2F used in our structural studies, residues 409-426 of E2F-1, represents the core of the pRb-binding region of the transcription factor. The structure shows that E2F binds at the interface of the A and B domains of the pocket making extensive interactions with conserved residues from both. We show by solution studies that a second site, probably contained within the "marked box" region of E2F, is responsible for additional interactions with the pRb pocket but is insufficient for complex formation on its own. In addition, we show that the interaction of the core binding fragment of E2F with pRb is inhibited by phosphorylation of the tumor suppressor protein by CDK2cyclin DE. Finally, our data reveal that the tight binding of the human papillomavirus E7 oncoprotein to pRb prevents subsequent interactions with the marked box region of E2F but not with its core binding region.
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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.