Suppression of the GTPase-activating protein RGS10 increases Rheb-GTP and mTOR signaling in ovarian cancer cells
The regulator of G protein signaling 10 (RGS10) protein is a GTPase activating protein that accelerates the hydrolysis of GTP and therefore canonically inactivates G proteins, ultimately terminating signaling. Rheb is a small GTPase protein that shuttles between its GDP- and GTP-bound forms to activate mTOR. Since RGS10 suppression augments ovarian cancer cell viability, we sought to elucidate the molecular mechanism. Following RGS10 suppression in serum-free conditions, phosphorylation of mTOR, the eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), p70S6K and S6 Ribosomal Protein appear. Furthermore, suppressing RGS10 increases activated Rheb, suggesting RGS10 antagonizes mTOR signaling via the small G-protein. The effects of RGS10 suppression are enhanced after stimulating cells with the growth factor, lysophosphatidic acid, and reduced with mTOR inhibitors, temsirolimus and INK-128. Suppression of RGS10 leads to an increase in cell proliferation, even in the presence of etoposide. In summary, the RGS10 suppression increases Rheb-GTP and mTOR signaling in ovarian cancer cells. Our results suggest that RGS10 could serve in a novel, and previously unknown, role by accelerating the hydrolysis of GTP from Rheb in ovarian cancer cells..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:369 |
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| Enthalten in: |
Cancer letters - 369(2015), 1, Seite 175 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Altman, Molly K [VerfasserIn] |
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| Links: |
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| doi: |
10.1016/j.canlet.2015.08.012 |
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| 100 | 1 | |a Altman, Molly K |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Suppression of the GTPase-activating protein RGS10 increases Rheb-GTP and mTOR signaling in ovarian cancer cells |
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| 520 | |a The regulator of G protein signaling 10 (RGS10) protein is a GTPase activating protein that accelerates the hydrolysis of GTP and therefore canonically inactivates G proteins, ultimately terminating signaling. Rheb is a small GTPase protein that shuttles between its GDP- and GTP-bound forms to activate mTOR. Since RGS10 suppression augments ovarian cancer cell viability, we sought to elucidate the molecular mechanism. Following RGS10 suppression in serum-free conditions, phosphorylation of mTOR, the eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), p70S6K and S6 Ribosomal Protein appear. Furthermore, suppressing RGS10 increases activated Rheb, suggesting RGS10 antagonizes mTOR signaling via the small G-protein. The effects of RGS10 suppression are enhanced after stimulating cells with the growth factor, lysophosphatidic acid, and reduced with mTOR inhibitors, temsirolimus and INK-128. Suppression of RGS10 leads to an increase in cell proliferation, even in the presence of etoposide. In summary, the RGS10 suppression increases Rheb-GTP and mTOR signaling in ovarian cancer cells. Our results suggest that RGS10 could serve in a novel, and previously unknown, role by accelerating the hydrolysis of GTP from Rheb in ovarian cancer cells. | ||
| 540 | |a Nutzungsrecht: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved. | ||
| 650 | 4 | |a Ovarian cancer | |
| 650 | 4 | |a mTOR | |
| 650 | 4 | |a American Recovery & Reinvestment Act 2009-US | |
| 650 | 4 | |a Studies | |
| 650 | 4 | |a Cell growth | |
| 650 | 4 | |a Kinases | |
| 650 | 4 | |a Regulator of G protein Signaling 10 protein (RGS10) | |
| 650 | 4 | |a Phosphorylation | |
| 650 | 4 | |a 4E-BP1 | |
| 650 | 4 | |a DNA methylation | |
| 650 | 4 | |a Proteins | |
| 650 | 4 | |a Rheb | |
| 650 | 4 | |a Lysophosphatidic acid | |
| 700 | 1 | |a Alshamrani, Ali A |4 oth | |
| 700 | 1 | |a Jia, Wei |4 oth | |
| 700 | 1 | |a Nguyen, Ha T |4 oth | |
| 700 | 1 | |a Fambrough, Jada M |4 oth | |
| 700 | 1 | |a Tran, Sterling K |4 oth | |
| 700 | 1 | |a Patel, Mihir B |4 oth | |
| 700 | 1 | |a Hoseinzadeh, Pooya |4 oth | |
| 700 | 1 | |a Beedle, Aaron M |4 oth | |
| 700 | 1 | |a Murph, Mandi M |4 oth | |
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| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/26319900 |
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