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Everolimus, sold under the brand name Afinitor among others, is a medication used as an immunosuppressant to prevent rejection of organ transplants and as a targeted therapy in the treatment of renal cell cancer and other tumours.
Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung disease, and kidney disease.
Lymphangioleiomyomatosis (LAM) is a rare, progressive and systemic disease that typically results in cystic lung destruction. It predominantly affects women, especially during childbearing years. The term sporadic LAM is used for patients with LAM not associated with tuberous sclerosis complex (TSC), while TSC-LAM refers to LAM that is associated with TSC.
Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration.
The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the MTOR gene. mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases.
Tuberous sclerosis 1 (TSC1), also known as hamartin, is a protein that in humans is encoded by the TSC1 gene.
Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the TSC2 gene.
RHEB also known as Ras homolog enriched in brain (RHEB) is a GTP-binding protein that is ubiquitously expressed in humans and other mammals. The protein is largely involved in the mTOR pathway and the regulation of the cell cycle.
Ribosomal protein S6 kinase alpha-1 is an enzyme that in humans is encoded by the RPS6KA1 gene.
Regulatory-associated protein of mTOR also known as raptor or KIAA1303 is an adapter protein that is encoded in humans by the RPTOR gene. Two mRNAs from the gene have been identified that encode proteins of 1335 and 1177 amino acids long.
DNA-damage-inducible transcript 4 (DDIT4) protein also known as protein regulated in development and DNA damage response 1 (REDD1) is a protein that in humans is encoded by the DDIT4 gene.
Rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR) is a protein that in humans is encoded by the RICTOR gene.
The Akt signaling pathway or PI3K-Akt signaling pathway is a signal transduction pathway that promotes survival and growth in response to extracellular signals. Key proteins involved are PI3K and Akt.
Tuberous sclerosis proteins 1 and 2, also known as TSC1 (hamartin) and TSC2 (tuberin), form a protein-complex. The encoding two genes are TSC1 and TSC2. The complex is known as a tumor suppressor. Mutations in these genes can cause tuberous sclerosis complex. Depending on the grade of the disease, intellectual disability, epilepsy and tumors of the skin, retina, heart, kidney and the central nervous system can be symptoms.
Lewis C. Cantley is an American cell biologist and biochemist who has made significant advances to the understanding of cancer metabolism. Among his most notable contributions are the discovery and study of the enzyme PI-3-kinase, now known to be important to understanding cancer and diabetes mellitus. He is currently Meyer Director and Professor of Cancer Biology at the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine in New York City. He was formerly a professor in the Departments of Systems Biology and Medicine at Harvard Medical School, and the Director of Cancer Research at the Beth Israel Deaconess Medical Center, in Boston, Massachusetts. In 2016, he was elected Chairman of the Board for the Hope Funds for Cancer Research.
mTOR inhibitors are a class of drugs that inhibit the mechanistic target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). mTOR regulates cellular metabolism, growth, and proliferation by forming and signaling through two protein complexes, mTORC1 and mTORC2. The most established mTOR inhibitors are so-called rapalogs, which have shown tumor responses in clinical trials against various tumor types.
mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrient/energy/redox sensor and controls protein synthesis.
mTOR Complex 2 (mTORC2) is an acutely rapamycin-insensitive protein complex formed by serine/threonine kinase mTOR that regulates cell proliferation and survival, cell migration and cytoskeletal remodeling. The complex itself is rather large, consisting of seven protein subunits. The catalytic mTOR subunit, DEP domain containing mTOR-interacting protein (DEPTOR), mammalian lethal with sec-13 protein 8, and TTI1/TEL2 complex are shared by both mTORC2 and mTORC1. Rapamycin-insensitive companion of mTOR (RICTOR), mammalian stress-activated protein kinase interacting protein 1 (mSIN1), and protein observed with rictor 1 and 2 (Protor1/2) can only be found mTORC2. Rictor has been shown to be the scaffold protein for substrate binding to mTORC2.
The Ragulator-Rag complex is a regulator of lysosomal signalling and trafficking in eukaryotic cells, which plays an important role in regulating cell metabolism and growth in response to nutrient availability in the cell. The Ragulator-Rag Complex is composed of five LAMTOR subunits, which work to regulate MAPK and mTOR complex 1. The LAMTOR subunits form a complex with Rag GTPase and v-ATPase, which sits on the cell’s lysosomes and detects the availability of amino acids. If the Ragulator complex receives signals for low amino acid count, it will start the process of catabolizing the cell. If there is an abundance of amino acids available to the cell, the Ragulator complex will signal that the cell can continue to grow. Ragulator proteins come in two different forms: Rag A/Rag B and Rag C/Rag D. These interact to form heterodimers with one another.
Immunometabolism is a branch of biology that studies the interplay between metabolism and immunology in all organisms. In particular, immunometabolism is the study of the molecular and biochemical underpinninngs for i) the metabolic regulation of immune function, and ii) the regulation of metabolism by molecules and cells of the immune system. Further categorization includes i) systemic immunometabolism and ii) cellular immunometabolism.
References
- 1 2 Dibble CC, Elis W, Menon S, Qin W, Klekota J, Asara JM, Finan PM, Kwiatkowski DJ, Murphy LO, Manning BD (2012). "TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1". Molecular Cell . 47 (4): 535–546. doi:10.1016/j.molcel.2012.06.009. PMC 3693578 . PMID 22795129.
- ↑ Menon S, Dibble CC, Talbott G, Hoxhaj G, Valvezan AJ, Takahashi H, Cantley LC, Manning BD (2014). "Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome". Cell . 156 (4): 771–785. doi:10.1016/j.cell.2013.11.049. PMC 403068 . PMID 24529379.
- ↑ Harputlugil E, Hine C, Vargas D, Robertson L, Manning BD, Mitchell JR (2014). "The TSC complex is required for the benefits of dietary protein restriction on stress resistance in vivo". Cell Reports . 8 (4): 1160–1170. doi:10.1016/j.celrep.2014.07.018. PMC 4260622 . PMID 25131199.
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