ArticleGenes & development2013
The retinoblastoma protein induces apoptosis directly at the mitochondria.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
83 citing papers in PubMed, 125 citations in OpenAlex.
- Trial
- Review
- A recently evolved domain of the human ING1 epigenetic regulator targets mitochondria and induces senescence.Cellular and molecular life sciences : CMLS · 2026Article
- Of Barriers and Loops-How Evolution Limits Most Cancer Risks to Older Ages.Cancer discovery · 2026Review
- Targeting LxCxE Cleft Pocket of Retinoblastoma Protein in Immunosuppressive Macrophages Inhibits Ovarian Cancer Progression.Cancer immunology research · 2025Article
- The tumor suppressor pRb and its relative p130 are required to maintain murine adult skeletal muscle homeostasis.Oncogene · 2025Article
- The Traditional Chinese Medicine FormulaJournal of Cancer · 2025Article
- CDK4/6 inhibition initiates cell cycle arrest by nuclear translocation of RB and induces a multistep molecular response.Cell death discovery · 2024Article
- Epstein-Barr virus replication within differentiated epithelia requires pRb sequestration of activator E2F transcription factors.Journal of virology · 2024Article
- Exploring the Antiproliferative and Modulatory Effects of 1-Methoxyisobrassinin on Ovarian Cancer Cells: Insights into Cell Cycle Regulation, Apoptosis, Autophagy, and Its Interactions with NAC.Molecules (Basel, Switzerland) · 2024Article
- Patterns in the tapestry of chromatin-bound RB.Trends in cell biology · 2024Review
- Methionine Supplementation Alleviates the Germ Cell Apoptosis Increased by Maternal Caffeine Intake in aNutrients · 2024Article
- Determinants for Antitumor and Protumor Effects of Programmed Cell Death.Cancer immunology research · 2024Article
- The significance ofFrontiers in immunology · 2024Review
- The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies.Life (Basel, Switzerland) · 2023Review
- Redox Properties, Bioactivity and Health Effects of Indicaxanthin, a Bioavailable Phytochemical fromAntioxidants (Basel, Switzerland) · 2022Review
- Interplay between Cell Death and Cell Proliferation Reveals New Strategies for Cancer Therapy.International journal of molecular sciences · 2022Review
- Hereditary retinoblastoma iPSC model reveals aberrant spliceosome function driving bone malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer.Cancer research · 2022Article
- Relevance of pRB Loss in Human Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The retinoblastoma protein gene RB-1 is mutated in one-third of human tumors. Its protein product, pRB (retinoblastoma protein), functions as a transcriptional coregulator in many fundamental cellular processes. Here, we report a nonnuclear role for pRB in apoptosis induction via pRB's direct participation in mitochondrial apoptosis. We uncovered this activity by finding that pRB potentiated TNFα-induced apoptosis even when translation was blocked. This proapoptotic function was highly BAX-dependent, suggesting a role in mitochondrial apoptosis, and accordingly, a fraction of endogenous pRB constitutively associated with mitochondria. Remarkably, we found that recombinant pRB was sufficient to trigger the BAX-dependent permeabilization of mitochondria or liposomes in vitro. Moreover, pRB interacted with BAX in vivo and could directly bind and conformationally activate BAX in vitro. Finally, by targeting pRB specifically to mitochondria, we generated a mutant that lacked pRB's classic nuclear roles. This mito-tagged pRB retained the ability to promote apoptosis in response to TNFα and also additional apoptotic stimuli. Most importantly, induced expression of mito-tagged pRB in Rb(-/-);p53(-/-) tumors was sufficient to block further tumor development. Together, these data establish a nontranscriptional role for pRB in direct activation of BAX and mitochondrial apoptosis in response to diverse stimuli, which is profoundly tumor-suppressive.
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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.