ArticleCell cycle (Georgetown, Tex.)2014
Phosphorylation of the Retinoblastoma protein (Rb) on serine-807 is required for association with Bax.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
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- Imipridones inhibit tumor growth and improve survival in an orthotopic liver metastasis mouse model of human uveal melanoma.British journal of cancer · 2024Article
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- Preclinical evaluation of the CDK4/6 inhibitor palbociclib in combination with a PI3K or MEK inhibitor in colorectal cancer.Cancer biology & therapy · 2023Article
- Protein post-translational modifications in the regulation of cancer hallmarks.Cancer gene therapy · 2023Review
- Bone Marrow Endothelial Cells Increase Prostate Cancer Cell Apoptosis in 3D Triculture Model of Reactive Stroma.Biology · 2022Article
- Post-translational modifications on the retinoblastoma protein.Journal of biomedical science · 2022Review
- Stress Relief Techniques: p38 MAPK Determines the Balance of Cell Cycle and Apoptosis Pathways.Biomolecules · 2021Review
- First in class dual MDM2/MDMX inhibitor ALRN-6924 enhances antitumor efficacy of chemotherapy in TP53 wild-type hormone receptor-positive breast cancer models.Breast cancer research : BCR · 2021Article
- Overlapping targets exist between the Par-4 and miR-200c axis which regulate EMT and proliferation of pancreatic cancer cells.Translational oncology · 2021Article
- Regulating tumor suppressor genes: post-translational modifications.Signal transduction and targeted therapy · 2020Review
- MCL1 binding to the reverse BH3 motif of P18INK4C couples cell survival to cell proliferation.Cell death & disease · 2020Article
- Crizotinib and PARP inhibitors act synergistically by triggering apoptosis in high-grade serous ovarian cancer.Oncotarget · 2019Article
- Drp1 and RB interaction to mediate mitochondria-dependent necroptosis induced by cadmium in hepatocytes.Cell death & disease · 2019Article
- G1/S cell cycle regulators mediate effects of circadian dysregulation on tumor growth and provide targets for timed anticancer treatment.PLoS biology · 2019Article
- Multiple Routes to Oncogenesis Are Promoted by the Human Papillomavirus-Host Protein Network.Cancer discovery · 2018Article
- The RASSF6 Tumor Suppressor Protein Regulates Apoptosis and Cell Cycle Progression via Retinoblastoma Protein.Molecular and cellular biology · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The recent finding that the Retinoblastoma protein (Rb) is able to regulate apoptosis in a non-transcriptional manner directly at the mitochondria by interaction with the pro-apoptotic protein Bax prompted this investigation of the complex formed between Rb and Bax. Because the function of Rb in the cellular processes of proliferation, apoptosis, senescence and differentiation is regulated by phosphorylation we endeavored to elucidate the phosphorylation status of Rb with respect to its association with Bax and its role in apoptosis. In this study we found that Rb phosphorylated on at least 4 C-terminal phosphorylation sites (S608, S795, S807/S811, and T821) is present at the mitochondria under non-stressed cellular conditions. An in vitro binding assay showed that Bax binds to Rb phosphorylated at S807/S811 in 3 cancer cell types. Physiologically relevant association between Bax and Rb phosphorylated on S807/S811 was demonstrated by reciprocal co-immunoprecipitation experiments using antibodies specific for Rb phosphorylated on S807/S811 and Bax. Mutant Rb proteins expressed in Rb-null C33A cells showed that phosphorylation of S807 of Rb promotes association with Bax and that mimicking phosphorylation at S807 of Rb can block the induction of apoptosis due to PNUTS downregulation. Finally using siRNA to activate phosphatase activity in MCF7 cells, Rb is dephosphorylated at several sites including S807/S811, dissociates from Bax and apoptosis is triggered. These studies show that phosphorylation of Rb regulates its association with Bax and its role in apoptosis.
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