File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1016/j.canlet.2015.08.012
- Scopus: eid_2-s2.0-84943455286
- PMID: 26319900
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Suppression of the GTPase-activating protein RGS10 increases Rheb-GTP and mTOR signaling in ovarian cancer cells
Title | Suppression of the GTPase-activating protein RGS10 increases Rheb-GTP and mTOR signaling in ovarian cancer cells |
---|---|
Authors | |
Keywords | 4E-BP1 Lysophosphatidic acid MTOR Regulator of G protein Signaling 10 protein (RGS10) Rheb |
Issue Date | 2015 |
Citation | Cancer Letters, 2015, v. 369, n. 1, p. 175-183 How to Cite? |
Abstract | 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. |
Persistent Identifier | http://hdl.handle.net/10722/342496 |
ISSN | 2021 Impact Factor: 9.756 2020 SCImago Journal Rankings: 2.470 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Altman, Molly K. | - |
dc.contributor.author | Alshamrani, Ali A. | - |
dc.contributor.author | Jia, Wei | - |
dc.contributor.author | Nguyen, Ha T. | - |
dc.contributor.author | Fambrough, Jada M. | - |
dc.contributor.author | Tran, Sterling K. | - |
dc.contributor.author | Patel, Mihir B. | - |
dc.contributor.author | Hoseinzadeh, Pooya | - |
dc.contributor.author | Beedle, Aaron M. | - |
dc.contributor.author | Murph, Mandi M. | - |
dc.date.accessioned | 2024-04-17T07:04:13Z | - |
dc.date.available | 2024-04-17T07:04:13Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Cancer Letters, 2015, v. 369, n. 1, p. 175-183 | - |
dc.identifier.issn | 0304-3835 | - |
dc.identifier.uri | http://hdl.handle.net/10722/342496 | - |
dc.description.abstract | 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. | - |
dc.language | eng | - |
dc.relation.ispartof | Cancer Letters | - |
dc.subject | 4E-BP1 | - |
dc.subject | Lysophosphatidic acid | - |
dc.subject | MTOR | - |
dc.subject | Regulator of G protein Signaling 10 protein (RGS10) | - |
dc.subject | Rheb | - |
dc.title | Suppression of the GTPase-activating protein RGS10 increases Rheb-GTP and mTOR signaling in ovarian cancer cells | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.canlet.2015.08.012 | - |
dc.identifier.pmid | 26319900 | - |
dc.identifier.scopus | eid_2-s2.0-84943455286 | - |
dc.identifier.volume | 369 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 175 | - |
dc.identifier.epage | 183 | - |
dc.identifier.eissn | 1872-7980 | - |