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Mitochondrial Unfolded Protein Response
The mitochondrial unfolded protein response (UPRmt) is a cellular stress response related to the mitochondria. The UPRmt results from Protein folding, unfolded or misfolded proteins in mitochondria beyond the capacity of Chaperone (protein), chaperone proteins to handle them. The UPRmt can occur either in the mitochondrial matrix or in the Inner mitochondrial membrane, mitochondrial inner membrane. In the UPRmt, the mitochondrion will either Downregulation and upregulation, upregulate chaperone proteins or invoke proteases to degrade proteins that fail to fold properly. UPRmt causes the sirtuin SIRT3 to activate Antioxidant#Enzyme systems, antioxidant enzymes and mitophagy. Mitochondrial electron transport chain mutations that extend the Maximum life span, life span of Caenorhabditis elegans (nematode worms) also activate the UPRmt. Activation of the UPRmt in nematode worms by increasing Nicotinamide adenine dinucleotide, NAD+ by supplementation with nicotinamide or nicotinamide ribo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cellular Stress Response
Cellular stress response is the wide range of molecular changes that cells undergo in response to environmental stressors, including extremes of temperature, exposure to toxins, and mechanical damage. Cellular stress responses can also be caused by some viral infections. The various processes involved in cellular stress responses serve the adaptive purpose of protecting a cell against unfavorable environmental conditions, both through short term mechanisms that minimize acute damage to the cell's overall integrity, and through longer term mechanisms which provide the cell a measure of resiliency against similar adverse conditions. General characteristics Cellular stress responses are primarily mediated through what are classified as ''stress proteins''. Stress proteins often are further subdivided into two general categories: those that only are activated by stress, or those that are involved both in stress responses and in normal cellular functioning. The essential character of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nicotinamide
Niacinamide or Nicotinamide (NAM) is a form of vitamin B3 found in food and used as a dietary supplement and medication. As a supplement, it is used by mouth to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) may be used for this purpose, niacinamide has the benefit of not causing skin flushing. As a cream, it is used to treat acne. It is a water-soluble vitamin. Niacinamide is the supplement name while Nicotinamide (NAM) is the scientific name. Side effects are minimal. At high doses liver problems may occur. Normal amounts are safe for use during pregnancy. Niacinamide is in the vitamin B family of medications, specifically the vitamin B3 complex. It is an amide of nicotinic acid. Foods that contain niacinamide include yeast, meat, milk, and green vegetables. Niacinamide was discovered between 1935 and 1937. It is on the World Health Organization's List of Essential Medicines. Niacinamide is available as a generic medication and over the c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Unfolded Protein Response
The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum (ER) stress. It has been found to be conserved between all mammalian species, as well as yeast and worm organisms. The UPR is activated in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum. In this scenario, the UPR has three aims: initially to restore normal function of the cell by halting protein translation, degrading misfolded proteins, and activating the signalling pathways that lead to increasing the production of molecular chaperones involved in protein folding. If these objectives are not achieved within a certain time span or the disruption is prolonged, the UPR aims towards apoptosis. Sustained overactivation of the UPR has been implicated in prion diseases as well as several other neurodegenerative diseases, and inhibiting the UPR could become a treatment for those diseases. Diseases amenable to UPR inhibition inc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ATF5
Activating transcription factor 5, also known as ATF5, is a protein that, in humans, is encoded by the ''ATF5'' gene. Function First described by Nishizawa and Nagata, ATF5 has been classified as a member of the activating transcription factor (ATF)/cAMP response-element binding protein (CREB) family. ATF5 transcripts and protein are expressed in a wide variety of tissues, in particular, high expression of transcripts in liver. It is also present in a variety of tumor cell types. ATF5 expression is regulated at both the transcriptional and translational level. ATF5 is expressed in VZ and SVZ during brain development. The human ATF5 protein is made up of 282 amino acids. ATF5 is a transcription factor that contains a bZip domain. See also * Activating transcription factor Interactions ATF5 has been shown to interact with DISC1 and TRIB3 Tribbles homolog 3 is a protein that in humans is encoded by the ''TRIB3'' gene. Function The protein encoded by this gene is a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Warburg Effect (oncology)
In oncology, the Warburg effect () is the observation that most cancer cells produce energy predominantly not through the 'usual' citric acid cycle and oxidative phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'aerobic glycolysis' consisting of high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not the mitochondria, even in the presence of abundant oxygen. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme". The precise mechanism and therapeutic implications of the Warburg effect, however, remain unclear. In fermentation, the last product of glycolysis, pyruvate, is converted into lactate (lactic acid fermentation) or ethanol (alcoholic fermentation). While fermentation produces adenosine triphosphate (ATP) only in low yield co ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sirtuin 3
NAD-dependent deacetylase sirtuin-3, mitochondrial also known as SIRT3 is a protein that in humans is encoded by the ''SIRT3'' gene irtuin (silent mating type information regulation 2 homolog) 3 (S. cerevisiae) SIRT3 is member of the mammalian sirtuin family of proteins, which are homologs to the yeast Sir2 protein. SIRT3 exhibits NAD+-dependent deacetylase activity. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes, and the protein encoded by this gene is included in class I of the sirtuin family. The human sirtuins have a range of molecular functions and have emerged as important proteins in aging, stress resistance and metabolic regulation. Yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. In addition to protein deacetylation, studies have shown that the human sirtuins may also function as intracellular regulatory proteins with mono ADP ribosyltransferase activity. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BZIP Domain
The Basic Leucine Zipper Domain (bZIP domain) is found in many DNA binding eukaryotic proteins. One part of the domain contains a region that mediates sequence specific DNA binding properties and the leucine zipper that is required to hold together (dimerize) two DNA binding regions. The DNA binding region comprises a number of basic amino acids such as arginine and lysine. Proteins containing this domain are transcription factors. bZIP transcription factors bZIP transcription factors are found in all eukaryotes and form one of the largest families of dimerizing TFs. An evolutionary study from 2008 revealed that 4 bZIP genes were encoded by the genome of the most recent common ancestor of all plants. Interactions between bZIP transcription factors are numerous and complex and play important roles in cancer development in epithelial tissues, steroid hormone synthesis by cells of endocrine tissues, factors affecting reproductive functions, and several other phenomena that aff ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Endoplasmic-reticulum-associated Protein Degradation
Endoplasmic-reticulum-associated protein degradation (ERAD) designates a cellular pathway which targets misfolded proteins of the endoplasmic reticulum for ubiquitination and subsequent degradation by a protein-degrading complex, called the proteasome. Mechanism The process of ERAD can be divided into three steps: Recognition of misfolded or mutated proteins in the endoplasmic reticulum The recognition of misfolded or mutated proteins depends on the detection of substructures within proteins such as exposed hydrophobic regions, unpaired cysteine residues and immature glycans. In mammalian cells for example, there exists a mechanism called glycan processing. In this mechanism, the lectin-type chaperones calnexin/calreticulin (CNX/CRT) provide immature glycoproteins the opportunity to reach their native conformation. They can do this by way of reglucosylating these glycoproteins by an enzyme called UDP-glucose- glycoprotein glucosyltransferase also known as UGGT. Term ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ATF6
Activating transcription factor 6, also known as ATF6, is a protein that, in humans, is encoded by the ''ATF6'' gene and is involved in the unfolded protein response. Function ATF6 is an endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ER molecules. Accumulation of misfolded proteins in the Endoplasmic Reticulum results in the proteolytic cleavage of ATF6. The cytosolic portion of ATF6 will move to the nucleus and act as a transcription factor to cause the transcription of ER chaperones. See also * Activating transcription factor Interactions ATF6 has been shown to interact with YY1 and Serum response factor Serum response factor, also known as SRF, is a transcription factor protein. Function Serum response factor is a member of the MADS (MCM1, Agamous, Deficiens, and SRF) box superfamily of transcription factors. This protein binds to the serum .... References Further reading * * * * * ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HSF1
Heat shock factor 1 (HSF1) is a protein that in humans is encoded by the ''HSF1'' gene. HSF1 is highly conserved in eukaryotes and is the primary mediator of transcriptional responses to proteotoxic stress with important roles in non-stress regulation such as development and metabolism. Structure Human HSF1 consists of several domains which regulate its binding and activity. DNA-Binding Domain (DBD) This N-terminal domain of approximately 100 amino acids is the most highly conserved region in the HSF protein family and consists of a helix-turn-helix loop. The DBD of each HSF1 monomer recognizes the sequence nGAAn on target DNA. Repeated sequences of the nGAAn pentamer constitute heat shock elements (HSEs) for active HSF1 trimers to bind. Oligomerization Domain (Leucine Zipper Domains) The two regions responsible for oligomerization between HSF1 monomers are leucine zipper (LZ) domains 1-3 and 4 (these regions are also commonly referred to as HR-A/B and HR-C). LZ1-3 is s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Proteostasis
Proteostasis is the dynamic regulation of a balanced, functional proteome. The proteostasis network includes competing and integrated biological pathways within cells that control the biogenesis, folding, trafficking, and degradation of proteins present within and outside the cell. Loss of proteostasis is central to understanding the cause of diseases associated with excessive protein misfolding and degradation leading to loss-of-function phenotypes, as well as aggregation-associated degenerative disorders. Therapeutic restoration of proteostasis may treat or resolve these pathologies. Cellular proteostasis is key to ensuring successful development, healthy aging, resistance to environmental stresses, and to minimize homeostatic perturbations from pathogens such as viruses. Cellular mechanisms for maintaining proteostasis include regulated protein translation, chaperone assisted protein folding, and protein degradation pathways. Adjusting each of these mechanisms based on the need f ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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