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Apoptosis Regulator Proteins, Bcl-2 Family
The Bcl-2 family (TC# 1.A.21) consists of a number of evolutionarily-conserved proteins that share Bcl-2 homology (BH) domains. The Bcl-2 family is most notable for their regulation of apoptosis, a form of programmed cell death, at the mitochondrion. The Bcl-2 family proteins consists of members that either promote or inhibit apoptosis, and control apoptosis by governing mitochondrial outer membrane permeabilization (MOMP), which is a key step in the intrinsic pathway of apoptosis. A total of 25 genes in the Bcl-2 family were identified by 2008. Members of the BCL-2 family regulate apoptosis in mammals, reptiles, amphibs, fish, and other phyla of metazoan life, with exception of nematodes and insects. Their molecular structure and function, as well as their protein dynamics, are highly conserved over hundreds of millions of years in tissue forming life forms. Structure Bcl-2 family proteins have a general structure that consists of a hydrophobic α-helix surrounded by amphi ...
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Conserved Sequence
In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids ( DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ( xenologous sequences). Conservation indicates that a sequence has been maintained by natural selection. A highly conserved sequence is one that has remained relatively unchanged far back up the phylogenetic tree, and hence far back in geological time. Examples of highly conserved sequences include the RNA components of ribosomes present in all domains of life, the homeobox sequences widespread amongst eukaryotes, and the tmRNA in bacteria. The study of sequence conservation overlaps with the fields of genomics, proteomics, evolutionary biology, phylogenetics, bioinformatics and mathematics. History The discovery of the role of DNA in heredity, and observations by Frederick Sanger of variation between animal insulins in 194 ...
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BH3 Interacting-domain Death Agonist
The BH3 interacting-domain death agonist, or BID, gene is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains (named BH1, BH2, BH3 and BH4), and can form hetero- or homodimers. Bcl-2 proteins act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Interactions BID is a pro-apoptotic Bcl-2 protein containing only the BH3 domain. In response to apoptotic signaling, BID interacts with another Bcl-2 family protein, Bax, leading to the insertion of Bax into organelle membranes, primarily the outer mitochondrial membrane. Bax is believed to interact with, and induce the opening of the mitochondrial voltage-dependent anion channel, VDAC. Alternatively, growing evidence suggest that activated Bax and/or Bak form an oligomeric pore, MAC in the outer membrane. This results in the release of cytochrome c and other pr ...
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Rho Family Of GTPases
The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants. Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. All G proteins are "molecular switches", and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions. History Identification of the Rho family of GTPases began in the mid-1980s. The first identified Rho member was RhoA, isolated serendipitously in 1985 from a low stringency cDNA screening. Rac1 and Rac2 were identified next, in 1989 followed by Cdc42 in 1990. Eight additional mammalian Rho members were identified from biological screenings until the late 1990s, a turning point in biology where availability of complete genome sequenc ...
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Cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into many compartments. In the eukaryotic cell, the cytosol is surrounded by the cell membrane and is part of the cytoplasm, which also comprises the mitochondria, plastids, and other organelles (but not their internal fluids and structures); the cell nucleus is separate. The cytosol is thus a liquid matrix around the organelles. In prokaryotes, most of the chemical reactions of metabolism take place in the cytosol, while a few take place in membranes or in the periplasmic space. In eukaryotes, while many metabolic pathways still occur in the cytosol, others take place within organelles. The cytosol is a complex mixture of substances dissolved in water. Although water forms the large majority of the cytosol, its structure and proper ...
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Calcium In Biology
Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a cofactor, including several of the coagulation factors. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation. Plasma calcium levels in mammals are tightly regulated, electronic-book electronic- with bone acting as the major mineral storage site. Calcium ions, Ca2+, are released from bone into the bloodstream under controlled conditions. Calcium is transported through the bloodstream as dissolved ions or bound to proteins such as serum albumin. Parathyroid hormone secreted by the parathyroid gland regulates the resorption of Ca2+ from bone, reabsorptio ...
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Mitochondrial Permeability Transition Pore
The mitochondrial permeability transition pore (mPTP or MPTP; also referred to as PTP, mTP, or MTP) is a protein pore complex that forms in the inner mitochondrial membrane under certain pathological conditions such as traumatic brain injury, ischemia, and stroke. Opening of the pore causes an increase in the permeability of the mitochondrial membrane to solutes with a molecular mass less than 1,500 daltons, leading to loss of membrane potential, swelling of the organelle, rupture of the outer membrane, and eventual cell death. The mPTP is thought to be regulated by multiple mitochondrial proteins. Historically, Cyclophilin D and the TSPO (formerly the peripheral benzodiazepine receptor) have been considered central components. In 2025, the AAA+ ATPase protein ATAD3A was identified as a novel upstream regulator of mPTP opening. Loss of ATAD3A was shown to prevent calcium-induced pore formation and render mitochondria insensitive to cyclosporin A, suggesting it acts upstream of ...
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Alternative Splicing
Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene may be included within or excluded from the final RNA product of the gene. This means the exons are joined in different combinations, leading to different splice variants. In the case of protein-coding genes, the proteins translated from these splice variants may contain differences in their amino acid sequence and in their biological functions (see Figure). Biologically relevant alternative splicing occurs as a normal phenomenon in eukaryotes, where it increases the number of proteins that can be encoded by the genome. In humans, it is widely believed that ~95% of multi-exonic genes are alternatively spliced to produce functional alternative products from the same gene but many scientists believe that most of the observed splice variants ar ...
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Protein Isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have unique functions. A set of protein isoforms may be formed from alternative splicings, variable promoter usage, or other post-transcriptional modifications of a single gene; post-translational modifications are generally not considered. (For that, see Proteoforms.) Through RNA splicing mechanisms, mRNA has the ability to select different protein-coding segments (exons) of a gene, or even different parts of exons from RNA to form different mRNA sequences. Each unique sequence produces a specific form of a protein. The discovery of isoforms could explain the discrepancy between the small number of protein coding regions of genes revealed by the human genome project and the large diversity of proteins seen in an organism: different proteins enc ...
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Bcl-xL
B-cell lymphoma-extra large (Bcl-xL), encoded by the BCL2-like 1 gene, is a transmembrane molecule in the mitochondria. It is a member of the Bcl-2 family of proteins, and acts as an anti-apoptotic protein by preventing the release of mitochondrial contents such as cytochrome c, which leads to caspase activation and ultimately, programmed cell death. Function It is a well-established concept in the field of apoptosis that relative amounts of pro- and anti-survival Bcl-2 family of proteins determine whether the cell will undergo cell death; if more Bcl-xL is present, then pores are non-permeable to pro-apoptotic molecules and the cell survives. However, if Bax and Bak become activated, and Bcl-xL is sequestered away by gatekeeper BH3-only factors (e.g. Bim) causing a pore to form, cytochrome c is released leading to initiation of caspase cascade and apoptotic events. While the exact signaling pathway of Bcl-xL is still not known, it is believed that Bcl-xL differs highly fr ...
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Growth Factor
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes. Growth factors typically act as signaling molecules between cells. Examples are cytokines and hormones that bind to specific receptors on the surface of their target cells. They often promote cell differentiation and maturation, which varies between growth factors. For example, epidermal growth factor (EGF) enhances osteogenic differentiation ( osteogenesis or bone formation), while fibroblast growth factors and vascular endothelial growth factors stimulate blood vessel differentiation ( angiogenesis). Comparison to cytokines ''Growth factor'' is sometimes used interchangeably among scientists with the term '' cytokine.'' Historically, cytokines were associated with hematopoietic (b ...
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