ArticleCell cycle (Georgetown, Tex.)2012
Dephosphorylation of threonine-821 of the retinoblastoma tumor suppressor protein (Rb) is required for apoptosis induced by UV and Cdk inhibition.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
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- Multi-OMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells.iScience · 2023Article
- The Four Homeostasis Knights: In Balance upon Post-Translational Modifications.International journal of molecular sciences · 2022Review
- 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
- Multiomics Analysis of Spatially Distinct Stromal Cells Reveals Tumor-Induced O-Glycosylation of the CDK4-pRB Axis in Fibroblasts at the Invasive Tumor Edge.Cancer research · 2022Article
- Fadraciclib (CYC065), a novel CDK inhibitor, targets key pro-survival and oncogenic pathways in cancer.PloS one · 2020Article
- A Code of Mono-phosphorylation Modulates the Function of RB.Molecular cell · 2019Article
- A System-wide Approach to Monitor Responses to Synergistic BRAF and EGFR Inhibition in Colorectal Cancer Cells.Molecular & cellular proteomics : MCP · 2018Article
- Article
- Detection of Retinoblastoma Protein Phosphorylation by Immunoblot Analysis.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Dephosphorylation of the Retinoblastoma protein (Rb) inhibits cancer cell EMT via Zeb.Cancer biology & therapy · 2016Article
- RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy.Oncotarget · 2015Review
- The retinoblastoma tumor suppressor modulates DNA repair and radioresponsiveness.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Phosphorylation of the Retinoblastoma protein (Rb) on serine-807 is required for association with Bax.Cell cycle (Georgetown, Tex.) · 2014Article
- Deciphering the retinoblastoma protein phosphorylation code.Trends in biochemical sciences · 2013Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The Retinoblastoma protein (Rb) is important in the control of cell proliferation and apoptosis. Its activity is controlled by reversible phosphorylation on several serine and threonine residues. When Rb is hypophosphorylated, it inhibits proliferation by preventing passage through the G 1- S phase transition. Hyperphosphorylated Rb promotes cell cycle progression. The role of Rb phosphorylation in the control of apoptosis is largely unknown, although several apoptotic stimuli result in dephosphorylation of Rb. It may be that dephosphorylation of specific amino acids signals apoptosis vs. cell cycle arrest. Using glutamic acid mutagenesis, we have generated 15 single phosphorylation site mutants of Rb to alter serine/threonine to glutamic acid to mimic the phosphorylated state. By calcium phosphate transfection, mutant plasmids were introduced into C33A Rb-null cells, and apoptosis was induced using UV. Apoptosis was measured by ELISA detection of degraded DNA and by immunoblotting to assess proteolytic cleavage of PARP. Our results show that only mutation of threonine-821 to glutamic acid (T821E) blocked apoptosis by 50%, whereas other sites tested had little effect. In Rb-null Saos-2 and SKUT-1 cells, the T821E mutation also blocked apoptosis induced by the cdk inhibitor, Roscovitine, by 50%. In addition, we show that endogenous Rb is dephosphorylated on threonine-821 when cells are undergoing apoptosis. Thus, our data indicates that dephosphorylation of threonine-821 of Rb is required for cells to undergo apoptosis.
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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.