Oxysterol-binding protein-related protein 5 (ORP5) promotes cell proliferation by activation of mTORC1 signaling
© 2018 by The American Society for Biochemistry and Molecular Biology, Inc..
Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a large family of proteins that mainly function in lipid transport and sensing. ORP5 is an endoplasmic reticulum (ER)-anchored protein implicated in lipid transfer at the contact sites between the ER and other membranes. Recent studies indicate that ORP5 is also involved in cancer cell invasion and tumor progression. However, the molecular mechanism underlying ORP5's involvement in cancer is unclear. Here, we report that ORP5 promotes cell proliferation and motility of HeLa cells, an effect that depends on its functional OSBP-related domain (ORD). We also found that ORP5 depletion or substitutions of key residues located within ORP5-ORD and responsible for interactions with lipids interfered with cell proliferation, migration, and invasion. ORP5 interacted with the protein mechanistic target of rapamycin (mTOR), and this interaction also required ORP5-ORD. Of note, whereas ORP5 overexpression induced mTOR complex 1 (mTORC1) activity, ORP5 down-regulation had the opposite effect. Finally, ORP5-depleted cells exhibited impaired mTOR localization to lysosomes, which may have accounted for the blunted mTORC1 activation. Together, our results suggest that ORP5 expression is positively correlated with mTORC1 signaling and that ORP5 stimulates cell proliferation, at least in part, by activating mTORC1.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:293 |
|---|---|
| Enthalten in: |
The Journal of biological chemistry - 293(2018), 10 vom: 09. März, Seite 3806-3818 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Du, Ximing [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 07.01.2019 Date Revised 04.12.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1074/jbc.RA117.001558 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM280199732 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM280199732 | ||
| 003 | DE-627 | ||
| 005 | 20231225024805.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1074/jbc.RA117.001558 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0934.xml |
| 035 | |a (DE-627)NLM280199732 | ||
| 035 | |a (NLM)29358326 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Du, Ximing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Oxysterol-binding protein-related protein 5 (ORP5) promotes cell proliferation by activation of mTORC1 signaling |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.01.2019 | ||
| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2018 by The American Society for Biochemistry and Molecular Biology, Inc. | ||
| 520 | |a Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a large family of proteins that mainly function in lipid transport and sensing. ORP5 is an endoplasmic reticulum (ER)-anchored protein implicated in lipid transfer at the contact sites between the ER and other membranes. Recent studies indicate that ORP5 is also involved in cancer cell invasion and tumor progression. However, the molecular mechanism underlying ORP5's involvement in cancer is unclear. Here, we report that ORP5 promotes cell proliferation and motility of HeLa cells, an effect that depends on its functional OSBP-related domain (ORD). We also found that ORP5 depletion or substitutions of key residues located within ORP5-ORD and responsible for interactions with lipids interfered with cell proliferation, migration, and invasion. ORP5 interacted with the protein mechanistic target of rapamycin (mTOR), and this interaction also required ORP5-ORD. Of note, whereas ORP5 overexpression induced mTOR complex 1 (mTORC1) activity, ORP5 down-regulation had the opposite effect. Finally, ORP5-depleted cells exhibited impaired mTOR localization to lysosomes, which may have accounted for the blunted mTORC1 activation. Together, our results suggest that ORP5 expression is positively correlated with mTORC1 signaling and that ORP5 stimulates cell proliferation, at least in part, by activating mTORC1 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ORP5 | |
| 650 | 4 | |a ORP8 | |
| 650 | 4 | |a OSBP | |
| 650 | 4 | |a cancer | |
| 650 | 4 | |a cell proliferation | |
| 650 | 4 | |a cell signaling | |
| 650 | 4 | |a lipids | |
| 650 | 4 | |a mTOR complex (mTORC) | |
| 650 | 4 | |a mammalian target of rapamycin (mTOR) | |
| 650 | 4 | |a phosphoinositide | |
| 650 | 7 | |a Neoplasm Proteins |2 NLM | |
| 650 | 7 | |a Receptors, Steroid |2 NLM | |
| 650 | 7 | |a Recombinant Fusion Proteins |2 NLM | |
| 650 | 7 | |a oxysterol binding protein |2 NLM | |
| 650 | 7 | |a Green Fluorescent Proteins |2 NLM | |
| 650 | 7 | |a 147336-22-9 |2 NLM | |
| 650 | 7 | |a MTOR protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.1.1 |2 NLM | |
| 650 | 7 | |a Mechanistic Target of Rapamycin Complex 1 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a TOR Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Zadoorian, Armella |e verfasserin |4 aut | |
| 700 | 1 | |a Lukmantara, Ivan E |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Yanfei |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Andrew J |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Hongyuan |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of biological chemistry |d 1945 |g 293(2018), 10 vom: 09. März, Seite 3806-3818 |w (DE-627)NLM000004995 |x 1083-351X |7 nnns |
| 773 | 1 | 8 | |g volume:293 |g year:2018 |g number:10 |g day:09 |g month:03 |g pages:3806-3818 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1074/jbc.RA117.001558 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 293 |j 2018 |e 10 |b 09 |c 03 |h 3806-3818 | ||