Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets
The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions via its discrete binding partners to form two multiprotein complexes, mTOR complex 1 and 2 (mTORC1 and mTORC2). Rapamycin-sensitive mTORC1, which regulates protein synthesis and cell growth, is tightly controlled...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/5/409 |
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| author | Meena Jhanwar-Uniyal Sabrina L. Zeller Eris Spirollari Mohan Das Simon J. Hanft Chirag D. Gandhi |
| author_facet | Meena Jhanwar-Uniyal Sabrina L. Zeller Eris Spirollari Mohan Das Simon J. Hanft Chirag D. Gandhi |
| author_sort | Meena Jhanwar-Uniyal |
| collection | DOAJ |
| description | The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions via its discrete binding partners to form two multiprotein complexes, mTOR complex 1 and 2 (mTORC1 and mTORC2). Rapamycin-sensitive mTORC1, which regulates protein synthesis and cell growth, is tightly controlled by PI3K/Akt and is nutrient-/growth factor-sensitive. In the brain, mTORC1 is also sensitive to neurotransmitter signaling. mTORC2, which is modulated by growth factor signaling, is associated with ribosomes and is insensitive to rapamycin. mTOR regulates stem cell and cancer stem cell characteristics. Aberrant Akt/mTOR activation is involved in multistep tumorigenesis in a variety of cancers, thereby suggesting that the inhibition of mTOR may have therapeutic potential. Rapamycin and its analogues, known as rapalogues, suppress mTOR activity through an allosteric mechanism that only suppresses mTORC1, albeit incompletely. ATP-catalytic binding site inhibitors are designed to inhibit both complexes. This review describes the regulation of mTOR and the targeting of its complexes in the treatment of cancers, such as glioblastoma, and their stem cells. |
| first_indexed | 2024-04-25T00:32:54Z |
| format | Article |
| id | doaj.art-07462b5f042c406781170e1feda5e21f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-25T00:32:54Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-07462b5f042c406781170e1feda5e21f2024-03-12T16:41:36ZengMDPI AGCells2073-44092024-02-0113540910.3390/cells13050409Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic TargetsMeena Jhanwar-Uniyal0Sabrina L. Zeller1Eris Spirollari2Mohan Das3Simon J. Hanft4Chirag D. Gandhi5Department of Neurosurgery, Westchester Medical Center, New York Medical College, Valhalla, NY 10595, USADepartment of Neurosurgery, Westchester Medical Center, New York Medical College, Valhalla, NY 10595, USADepartment of Neurosurgery, Westchester Medical Center, New York Medical College, Valhalla, NY 10595, USADepartment of Neurosurgery, Westchester Medical Center, New York Medical College, Valhalla, NY 10595, USADepartment of Neurosurgery, Westchester Medical Center, New York Medical College, Valhalla, NY 10595, USADepartment of Neurosurgery, Westchester Medical Center, New York Medical College, Valhalla, NY 10595, USAThe mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions via its discrete binding partners to form two multiprotein complexes, mTOR complex 1 and 2 (mTORC1 and mTORC2). Rapamycin-sensitive mTORC1, which regulates protein synthesis and cell growth, is tightly controlled by PI3K/Akt and is nutrient-/growth factor-sensitive. In the brain, mTORC1 is also sensitive to neurotransmitter signaling. mTORC2, which is modulated by growth factor signaling, is associated with ribosomes and is insensitive to rapamycin. mTOR regulates stem cell and cancer stem cell characteristics. Aberrant Akt/mTOR activation is involved in multistep tumorigenesis in a variety of cancers, thereby suggesting that the inhibition of mTOR may have therapeutic potential. Rapamycin and its analogues, known as rapalogues, suppress mTOR activity through an allosteric mechanism that only suppresses mTORC1, albeit incompletely. ATP-catalytic binding site inhibitors are designed to inhibit both complexes. This review describes the regulation of mTOR and the targeting of its complexes in the treatment of cancers, such as glioblastoma, and their stem cells.https://www.mdpi.com/2073-4409/13/5/409mTORmTORC1mTORC2S6K4E-BP1GBM |
| spellingShingle | Meena Jhanwar-Uniyal Sabrina L. Zeller Eris Spirollari Mohan Das Simon J. Hanft Chirag D. Gandhi Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets Cells mTOR mTORC1 mTORC2 S6K 4E-BP1 GBM |
| title | Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets |
| title_full | Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets |
| title_fullStr | Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets |
| title_full_unstemmed | Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets |
| title_short | Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets |
| title_sort | discrete mechanistic target of rapamycin signaling pathways stem cells and therapeutic targets |
| topic | mTOR mTORC1 mTORC2 S6K 4E-BP1 GBM |
| url | https://www.mdpi.com/2073-4409/13/5/409 |
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