ArticleOncogene2018
RBL2/p130 is a direct AKT target and is required to induce apoptosis upon AKT inhibition in lung cancer and mesothelioma cell lines.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
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- A robust EMT-related prognostic model for ccRCC integrating single-cell and bulk transcriptome data.Discover oncology · 2025Article
- Clinical and genetic characterization of a progressive RBL2-associated neurodevelopmental disorder.Brain : a journal of neurology · 2025Article
- A new signature associated with anoikis predicts the outcome and immune infiltration in nasopharyngeal carcinoma.Discover oncology · 2025Article
- Caprine herpes virus-1 reduces cell viability and enhances chemosensitivity in breast cancer cells.Frontiers in oncology · 2025Article
- Pharmacological inhibition of CDK4/6 impairs diffuse pleural mesothelioma 3D spheroid growth and reduces viability of cisplatin-resistant cells.Frontiers in oncology · 2024Article
- Loss of Rbl2 (Retinoblastoma-Like 2) Exacerbates Myocardial Ischemia/Reperfusion Injury.Journal of the American Heart Association · 2022Article
- Independent effects of Src kinase and podoplanin on anchorage independent cell growth and migration.Molecular carcinogenesis · 2022Article
- Advancements in the identification of EV derived mRNA biomarkers for liquid biopsy of clear cell renal cell carcinomas.Urology · 2022Article
- Deciphering the Effects and Mechanisms of Yi-Fei-San-Jie-pill on Non-Small Cell Lung Cancer With Integrating Network Target Analysis and Experimental Validation.Frontiers in pharmacology · 2022Article
- RB1 Is an Immune-Related Prognostic Biomarker for Ovarian Cancer.Frontiers in oncology · 2022Article
- Article
- TTPAL promotes gastric tumorigenesis by directly targeting NNMT to activate PI3K/AKT signaling.Oncogene · 2021Article
- Article
- Gene expression profiling after LINC00472 overexpression in an NSCLC cell line1.Cancer biomarkers : section A of Disease markers · 2021Article
- HAX1 enhances the survival and metastasis of non-small cell lung cancer through the AKT/mTOR and MDM2/p53 signaling pathway.Thoracic cancer · 2020Article
- Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of theInternational journal of molecular sciences · 2020Article
- Review
- PRMT5 silencing selectively affects MTAP-deleted mesothelioma: In vitro evidence of a novel promising approach.Journal of cellular and molecular medicine · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The retinoblastoma (RB) protein family includes RB1/p105, RBL1/p107, and RBL2/p130, which are key factors in cell-cycle regulation and stand at the crossroads of multiple pathways dictating cell fate decisions. The role of RB proteins in apoptosis is controversial because they can inhibit or promote apoptosis depending on the context, on the apoptotic stimuli and on their intrinsic status, impacting on the response to antitumoral treatments. Here we identified RBL2/p130 as a direct substrate of the AKT kinase, a key antiapoptotic factor hyperactive in multiple cancer types. We showed that RBL2/p130 and AKT1 physically interact and AKT phosphorylates RBL2/p130 Ser941, located in the pocket domain, but not when this residue is mutated into Ala. We found that pharmacological inhibition of AKT, through the highly selective AKT inhibitor VIII (AKTiVIII), impairs RBL2/p130 Ser941 phosphorylation and increases RBL2/p130 stability, mRNA expression and nuclear levels in both lung cancer and mesothelioma cell lines, mirroring the more extensively studied effects on the p27 cell-cycle inhibitor. Consistently, AKT inhibition reduced cell viability, induced cell accumulation in G0/G1, and triggered apoptosis, which proved to be largely dependent on RBL2/p130 itself, as shown upon RBL2/p130 silencing. AKT inhibition induced RBL2/p130-dependent apoptosis also in HEK-293 cells, in which re-expression of a short hairpin-resistant RBL2/p130 was able to rescue AKTiVIII-induced apoptosis upon RBL2/p130 silencing. Our data also showed that the combination of AKT and cyclin-dependent kinases (CDK) inhibitors, which converge on the re-activation of RBL2/p130 antitumoral potential, could be a promising anticancer strategy.
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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.