Suppression of the GTPase-activating protein RGS10 increases Rheb-GTP and mTOR signaling in ovarian cancer cells
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved..
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: |
E-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 vom: 01. Dez., Seite 175-83 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Altman, Molly K [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.02.2016 Date Revised 03.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.canlet.2015.08.012 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM252282167 |
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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 |
| 264 | 1 | |c 2015 | |
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| 500 | |a Date Revised 03.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2015 Elsevier Ireland Ltd. All rights reserved. | ||
| 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, American Recovery and Reinvestment Act | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 4E-BP1 | |
| 650 | 4 | |a Lysophosphatidic acid | |
| 650 | 4 | |a Regulator of G protein Signaling 10 protein (RGS10) | |
| 650 | 4 | |a Rheb | |
| 650 | 4 | |a mTOR | |
| 650 | 7 | |a Neuropeptides |2 NLM | |
| 650 | 7 | |a RGS Proteins |2 NLM | |
| 650 | 7 | |a RGS10 protein, human |2 NLM | |
| 650 | 7 | |a RHEB protein, human |2 NLM | |
| 650 | 7 | |a Ras Homolog Enriched in Brain Protein |2 NLM | |
| 650 | 7 | |a MTOR protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.1.1 |2 NLM | |
| 650 | 7 | |a TOR Serine-Threonine Kinases |2 NLM | |
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| 650 | 7 | |a Monomeric GTP-Binding Proteins |2 NLM | |
| 650 | 7 | |a EC 3.6.5.2 |2 NLM | |
| 700 | 1 | |a Alshamrani, Ali A |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Ha T |e verfasserin |4 aut | |
| 700 | 1 | |a Fambrough, Jada M |e verfasserin |4 aut | |
| 700 | 1 | |a Tran, Sterling K |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Mihir B |e verfasserin |4 aut | |
| 700 | 1 | |a Hoseinzadeh, Pooya |e verfasserin |4 aut | |
| 700 | 1 | |a Beedle, Aaron M |e verfasserin |4 aut | |
| 700 | 1 | |a Murph, Mandi M |e verfasserin |4 aut | |
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