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DDIT4
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. Function DDIT4 acts as a negative regulator of mTOR, a serine/threonine kinase that regulates a variety of cellular functions such as growth, proliferation and autophagy. In particular, upregulation of HIF-1 in response to hypoxia upregulates DDIT4, leading to activation of Tsc1/2 via 14–3–3 shuttling and subsequent downregulation of mTOR via Rheb. In addition to hypoxia, DDIT4 expression has also been shown to be activated by DNA damage and energy stress. Clinical significance Clinical interest in DDIT4 is based primarily on its effect on mTOR, which has been associated with aging and linked with diseases such as tuberous sclerosis, lymphangioleiomyomatosis, diabetes, and cancer. In particular, the overactivation of mTOR in many cancer types has led to the development of mT ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tuberous Sclerosis Protein
Tuberous sclerosis proteins 1 and 2, also known as TSC1 (hamartin) and TSC2 (tuberin), form a protein-complex that functions as a GAP for Rheb. 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. Physiological roles The TSC1/TSC2-complex integrates environmental signals such as stress and energy status in yeast and stress, energy status and growth factors in mammals into TOR signalling. In the case of stress (DNA damage, hypoxia) or low energy availability, it is activated and regulates protein synthesis down. Growth factors lead to an inhibition of the complex and have a positive effect on protein synthesis. Defects in its genes result in less control of cell growth and may cause tuberous sclerosis or tuberous sclerosis complex (TSC). TSC is a rare geneti ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabolic reactions, DNA replication, Cell signaling, responding to stimuli, providing Cytoskeleton, structure to cells and Fibrous protein, organisms, and Intracellular transport, transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the Nucleic acid sequence, nucleotide sequence of their genes, and which usually results in protein folding into a specific Protein structure, 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called pep ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and non-coding genes. During gene expression (the synthesis of Gene product, RNA or protein from a gene), DNA is first transcription (biology), copied into RNA. RNA can be non-coding RNA, directly functional or be the intermediate protein biosynthesis, template for the synthesis of a protein. The transmission of genes to an organism's offspring, is the basis of the inheritance of phenotypic traits from one generation to the next. These genes make up different DNA sequences, together called a genotype, that is specific to every given individual, within the gene pool of the population (biology), population of a given species. The genotype, along with environmental and developmental factors, ultimately determines the phenotype ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MTOR
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. mTOR links with other proteins and serves as a core component of two distinct protein complexes, mTOR complex 1 and mTOR complex 2, which regulate different cellular processes. In particular, as a core component of both complexes, mTOR functions as a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. As a core component of mTORC2, mTOR also functions as a tyrosine protein kinase that promotes the activation of insulin receptors and insulin-like growth factor 1 receptors. mTORC2 has also been implicated in the control and maintenanc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HIF1A
Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 ( HIF-1) that is encoded by the ''HIF1A'' gene. The Nobel Prize in Physiology or Medicine 2019 was awarded for the discovery of HIF. HIF1A is a basic helix-loop-helix PAS domain containing protein, and is considered as the master transcriptional regulator of cellular and developmental response to hypoxia. The dysregulation and overexpression of ''HIF1A'' by either hypoxia or genetic alternations have been heavily implicated in cancer biology, as well as a number of other pathophysiologies, specifically in areas of vascularization and angiogenesis, energy metabolism, cell survival, and tumor invasion. The presence of HIF1A in a hypoxic environment is required to push forward normal placental development in early gestation. Two other alternative transcripts encoding different isoforms have been identified. Structure HIF1 is a het ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tumor Hypoxia
Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic microenvironments in solid tumors are a result of available oxygen being consumed within 70 to 150 μm of tumor vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue. In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism. Furthermore, hypoxia is known to change cell behavior and is associated with extracellular matrix remodeling and increased migratory and metastatic behavior. Changes in the glycolytic pathway A particular change in metabolism, historically known as the Warburg effect results in high rates of glycolysis in both normoxic and hypoxic c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
14-3-3 Protein
14-3-3 proteins are a family of conserved regulatory molecules that are expressed in all eukaryotic cells. 14-3-3 proteins have the ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors. More than 200 signaling proteins have been reported as 14-3-3 ligands. Elevated amounts of 14-3-3 protein in cerebrospinal fluid are usually a sign of rapid neurodegeneration; a common indicator of Creutzfeldt–Jakob disease. Properties Seven genes encode seven distinct 14-3-3 proteins in most mammals (See ''Human genes'' below) and 13-15 genes in many higher plants, though typically in fungi they are present only in pairs. Protists have at least one. Eukaryotes can tolerate the loss of a single 14-3-3 gene if multiple genes are expressed, but deletion of all 14-3-3s (as experimentally determined in yeast) results in death. 14-3-3 proteins are structurally similar to the Tetratrico Peptide Repeat (TPR) superfa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tuberous Sclerosis
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. TSC is caused by a mutation of either of two genes, '' TSC1'' and '' TSC2'', which code for the proteins hamartin and tuberin, respectively, with ''TSC2'' mutations accounting for the majority and tending to cause more severe symptoms. These proteins act as tumor growth suppressors, agents that regulate cell proliferation and differentiation. Prognosis is highly variable and depends on the symptoms, but life expectancy is normal for many. The prevalence of the disease is estimated to be 7 to 12 in 100,000. The disease is often abbreviated to tuberous sclerosis, which refers to t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lymphangioleiomyomatosis
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. Signs and symptoms The average age of onset is the early-to-mid-30s. Exertional dyspnea (shortness of breath) and spontaneous pneumothorax (lung collapse) have been reported as the initial presentation of the disease in 49% and 46% of patients, respectively. Diagnosis is typically delayed 5 to 6 years. The condition is often misdiagnosed as asthma or chronic obstructive pulmonary disease. The first pneumothorax, or lung collapse, precedes the diagnosis of LAM in 82% of patients. The consensus clinical definition of LAM includes multiple symptoms: * Fatigue * Cough * Hemoptysis, Coughing up blood (rarely massive) * Chest pain * ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Diabetes Mellitus
Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of the body becoming unresponsive to insulin's effects. Classic symptoms include polydipsia (excessive thirst), polyuria (excessive urination), polyphagia (excessive hunger), Weight loss#Unintentional, weight loss, and blurred vision. If left untreated, the disease can lead to various health complications, including disorders of the Cardiovascular disease, cardiovascular system, Diabetic retinopathy, eye, Diabetic nephropathy, kidney, and Diabetic neuropathy, nerves. Diabetes accounts for approximately 4.2 million deaths every year, with an estimated 1.5 million caused by either untreated or poorly treated diabetes. The major types of diabetes are Type 1 diabetes, type 1 and Type 2 diabetes, type 2. The most common treatment for ty ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible Signs and symptoms of cancer, signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in defecation, bowel movements. While these symptoms may indicate cancer, they can also have other causes. List of cancer types, Over 100 types of cancers affect humans. Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor Diet (nutrition), diet, sedentary lifestyle, lack of physical activity or Alcohol abuse, excessive alcohol consumption. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. infectious causes of cancer, Infection with specific viruses, bacteria and parasites is an environmental factor cau ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
