Journal article
Two for the Price of One: G Protein-Dependent and -Independent Functions of RGS6 In Vivo
Progress in molecular biology and translational science, Vol.133, pp.123-151
2015
DOI: 10.1016/bs.pmbts.2015.03.001
PMID: 26123305
Abstract
Regulator of G protein signaling 6 (RGS6) is unique among the members of the RGS protein family as it remains the only protein with the demonstrated capacity to control G protein-dependent and -independent signaling cascades in vivo. RGS6 inhibits signaling mediated by γ-aminobutyric acid B receptors, serotonin 1A receptors, μ opioid receptors, and muscarinic acetylcholine 2 receptors. RGS6 deletion triggers distinct behavioral phenotypes resulting from potentiated signaling by these G protein-coupled receptors namely ataxia, a reduction in anxiety and depression, enhanced analgesia, and increased parasympathetic tone, respectively. In addition, RGS6 possesses potent proapoptotic and growth suppressive actions. In heart, RGS6-dependent reactive oxygen species (ROS) production promotes doxorubicin (Dox)-induced cardiomyopathy, while in cancer cells RGS6/ROS signaling is necessary for activation of the ataxia telangiectasia mutated/p53/apoptosis pathway required for the chemotherapeutic efficacy of Dox. Further, by facilitating Tip60 (trans-acting regulator protein of HIV type 1-interacting protein 60 kDa)-dependent DNA methyltransferase 1 degradation, RGS6 suppresses cellular transformation in response to oncogenic Ras. The culmination of these G protein-independent actions results in potent tumor suppressor actions of RGS6 in the murine mammary epithelium. This work summarizes evidence from human genetic studies and model animals implicating RGS6 in normal physiology, disease, and the pharmacological actions of multiple drugs. Though efforts by multiple laboratories have contributed to the ever-growing RGS6 oeuvre, the pleiotropic nature of this gene will likely lead to additional work detailing the importance of RGS6 in neuropsychiatric disorders, cardiovascular disease, and cancer.
Details
- Title: Subtitle
- Two for the Price of One: G Protein-Dependent and -Independent Functions of RGS6 In Vivo
- Creators
- Adele Stewart - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USABiswanath Maity - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USARory A Fisher - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA. Electronic address: rory-fisher@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Progress in molecular biology and translational science, Vol.133, pp.123-151
- Publisher
- Netherlands
- DOI
- 10.1016/bs.pmbts.2015.03.001
- PMID
- 26123305
- ISSN
- 1877-1173
- eISSN
- 1878-0814
- Grant note
- CA161882 / NCI NIH HHS R01 CA161882 / NCI NIH HHS T32 MH065215 / NIMH NIH HHS
- Language
- English
- Date published
- 2015
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040589802771
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