Tuberous sclerosis 1 (TSC1), also known as hamartin, is a protein that in humans is encoded by the TSC1 gene. [5]
Tuberous sclerosis 1 (TSC1), also known as hamartin, is a protein that in humans is encoded by the TSC1 gene. [5]
TSC1 functions as a co-chaperone which inhibits the ATPase activity of the chaperone Hsp90 (heat shock protein-90) and decelerates its chaperone cycle. TSC1 functions as a facilitator of Hsp90 in chaperoning the kinase and non-kinase clients including TSC2, therefore preventing their ubiquitination and degradation in the proteasome. [6] TSC1, TSC2 and TBC1D7 is a multi-protein complex also known as the TSC complex. This complex negatively regulates mTORC1 signaling by functioning as a GTPase-activating protein (GAP) for the small GTPase Rheb, an essential activator of mTORC1. The TSC complex has been implicated as a tumor suppressor.
Defects in this gene can cause tuberous sclerosis, due to a functional impairment of the TSC complex.[ citation needed ] Defects in TSC1 may also be a cause of focal cortical dysplasia.[ citation needed ] TSC1 may be involved in protecting brain neurons in the CA3 region of the hippocampus from the effects of stroke. [7]
TSC1 has been shown to interact with:
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.
A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize. Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have relatively well differentiated cells. They are often surrounded by an outer surface or stay contained within the epithelium. Common examples of benign tumors include moles and uterine fibroids.
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.
Phakomatoses, also known as neurocutaneous syndromes, are a group of multisystemic diseases that most prominently affect structures primarily derived from the ectoderm such as the central nervous system, skin and eyes. The majority of phakomatoses are single-gene disorders that may be inherited in an autosomal dominant, autosomal recessive or X-linked pattern. Presentations may vary dramatically between patients with the same particular syndrome due to mosaicism, variable expressivity, and penetrance.
Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells.
Tuberous sclerosis complex (TSC) tumor suppressors form the TSC1-TSC2 molecular complex. Under poor growth conditions the TSC1-TSC2 complex limits cell growth. A key promoter of cell growth, mTORC1, is inhibited by the tuberous sclerosis complex. Insulin activates mTORC1 and causes dissociation of TSC from the surface of lysosomes.
Angiomyolipomas are the most common benign tumour of the kidney. Although regarded as benign, angiomyolipomas may grow such that kidney function is impaired or the blood vessels may dilate and burst, leading to bleeding.
The history of tuberous sclerosis (TSC) research spans less than 200 years. TSC is a rare, multi-system genetic disease that can cause benign tumours to grow on the brain or other vital organs such as the kidneys, heart, eyes, lungs, and skin. A combination of symptoms may include seizures, developmental delay, behavioural problems and skin abnormalities, as well as lung and kidney disease. TSC is caused by mutations on either of two genes, TSC1 and TSC2, which encode for the proteins hamartin and tuberin respectively. These proteins act as tumour growth suppressors and regulate cell proliferation and differentiation. Originally regarded as a rare pathological curiosity, it is now an important focus of research into tumour formation and suppression.
The tumor suppressor gene FLCN encodes the protein folliculin, also known as Birt–Hogg–Dubé syndrome protein, which functions as an inhibitor of Lactate Dehydrogenase-A and a regulator of the Warburg effect. Folliculin (FLCN) is also associated with Birt–Hogg–Dubé syndrome, which is an autosomal dominant inherited cancer syndrome in which affected individuals are at risk for the development of benign cutaneous tumors (folliculomas), pulmonary cysts, and kidney tumors.
Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the PLK1 gene.
Tuberous sclerosis complex 2 (TSC2), also known as tuberin, is a protein that in humans is encoded by the TSC2 gene.
Ras-related protein Rap-1A is a protein that in humans is encoded by the RAP1A 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.
RB1-inducible coiled-coil protein 1 is a protein that in humans is encoded by the RB1CC1 gene.
Dedicator of cytokinesis protein (Dock7) is a large protein encoded in the human by the DOCK7 gene, involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G-proteins. Dock7 activates isoforms of the small G protein Rac.
Koenen's tumor (KT), also commonly termed periungual angiofibroma, is a subtype of the angiofibromas. Angiofibromas are benign papule, nodule, and/or tumor lesions that are separated into various subtypes based primarily on the characteristic locations of their lesions. KTs are angiofibromas that develop in and under the toenails and/or fingernails. KTs were once considered as the same as another subtype of the angiofibromas viz., acral angiofibromas. While the literature may still sometimes regard KTs as acral angiofibromas, acral angiofibromas are characteristically located in areas close to but not in the toenails and fingernails as well as in the soles of the feet and palms of the hands. KTs are here regarded as distinct from acral angiofibromas.
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.
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.
Alcino J. Silva is a Portuguese-American neuroscientist who was the recipient of the 2008 Order of Prince Henry and elected as a fellow of the American Association for the Advancement of Science in 2013 for his contributions to the molecular cellular cognition of memory, a field he pioneered with the publication of two articles in Science in 1992.
Duojia Pan is a Chinese-American developmental biologist at the University of Texas Southwestern Medical Center, where he is Fouad A. and Val Imm Bashour Distinguished Professor of Physiology, chairman of the department of physiology, and investigator of the Howard Hughes Medical Institute (HHMI). His research is focused on molecular mechanisms of growth control and tissue homeostasis and their implications in human disease.