ArticleCancer research2011
Regulator of G protein signaling 6 mediates doxorubicin-induced ATM and p53 activation by a reactive oxygen species-dependent mechanism.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The trial behind it
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
43 citing papers in PubMed, 88 citations in OpenAlex.
- In vivo effects of dexamethasone on blood gene expression in ataxia telangiectasia.Molecular and cellular biochemistry · 2018Trial
- Review
- Haplotype-resolved de novo assembly revealed unique characteristics of alternative lengthening of telomeres in mouse embryonic stem cells.Nucleic acids research · 2024Article
- RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21.Journal of translational medicine · 2024Article
- Regulator of G protein signaling protein 6 alleviates acute lung injury by inhibiting inflammation and promoting cell self-renewal in mice.Cellular & molecular biology letters · 2023Article
- RGS7 balances acetylation/de-acetylation of p65 to control chemotherapy-dependent cardiac inflammation.Cellular and molecular life sciences : CMLS · 2023Article
- RGS proteins and their roles in cancer: friend or foe?Cancer cell international · 2023Review
- A RGS7-CaMKII complex drives myocyte-intrinsic and myocyte-extrinsic mechanisms of chemotherapy-induced cardiotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- RGS6 suppresses TGF-β-induced epithelial-mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4.Cell death & disease · 2022Article
- Self-assembled dipeptide based fluorescent nanoparticles as a platform for developing cellular imaging probes and targeted drug delivery chaperones.Nanoscale advances · 2022Article
- NMCP-2 polysaccharide purified fromFood science & nutrition · 2021Article
- Hepatic Regulator of G Protein Signaling 6 (RGS6) drives non-alcoholic fatty liver disease by promoting oxidative stress and ATM-dependent cell death.Redox biology · 2021Article
- G Protein-Coupled receptors and heterotrimeric G proteins as cancer drivers.FEBS letters · 2020Review
- Regulator of G-protein signaling (RGS) proteins as drug targets: Progress and future potentials.The Journal of biological chemistry · 2019Review
- Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses.The EMBO journal · 2019Article
- Regulator of G Protein Signaling 6 Facilities Cardiac Hypertrophy by Activating Apoptosis Signal-Regulating Kinase 1-P38/c-JUN N-Terminal Kinase 1/2 Signaling.Journal of the American Heart Association · 2018Article
- G Protein-Coupled Receptor Systems as Crucial Regulators of DNA Damage Response Processes.International journal of molecular sciences · 2018Review
- RGS7 is recurrently mutated in melanoma and promotes migration and invasion of human cancer cells.Scientific reports · 2018Article
- Regulating the regulators: Epigenetic, transcriptional, and post-translational regulation of RGS proteins.Cellular signalling · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Doxorubicin (DXR), among the most widely used cancer chemotherapy agents, promotes cancer cell death via activation of ataxia telangiectasia mutated (ATM) and the resultant upregulation of tumor suppressor p53. The exact mechanism by which DXR activates ATM is not fully understood. Here, we discovered a novel role for regulator of G protein signaling 6 (RGS6) in mediating activation of ATM and p53 by DXR. RGS6 was robustly induced by DXR, and genetic loss of RGS6 dramatically impaired DXR-induced activation of ATM and p53, as well as its in vivo apoptotic actions in heart. The ability of RGS6 to promote p53 activation in response to DXR was independent of RGS6 interaction with G proteins but required ATM. RGS6 mediated activation of ATM and p53 by DXR via a reactive oxygen species (ROS)-dependent and DNA damage-independent mechanism. This mechanism represents the primary means by which DXR promotes activation of the ATM-p53 apoptosis pathway that underlies its cytotoxic activity. Our findings contradict the canonical theories that DXR activates ATM primarily by promoting DNA damage either directly or indirectly (via ROS) and that RGS6 function is mediated by its interactions with G proteins. These findings reveal a new mechanism for the chemotherapeutic actions of DXR and identify RGS6 as a novel target for cancer chemotherapy.
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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.