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Adenovirus E1B Protein
Adenovirus E1B protein usually refers to one of two proteins transcribed from the E1B gene of the adenovirus: a 55kDa protein and a 19kDa protein. These two proteins are needed to block apoptosis in adenovirus-infected cells. E1B proteins work to prevent apoptosis that is induced by the small adenovirus E1A protein, which stabilizes p53, a tumor suppressor. Functions E1B-19k E1B-19k blocks a p53-independent apoptosis mechanism. Without E1B-19k, degradation of both cellular and viral DNA occurs, in addition to premature host cell death during the lytic cycle, thus limiting viral replication. E1B-19k mimics MCL1, which is a cellular antiapoptotic protein. In infected cells, the expression of E1A results in the degradation of MCL-1, which normally binds the propaptotic protein, BAK. BAK activation induces apoptosis by cooligomerizing with another proapoptotic protein, BAX. Together, BAK and BAX form pores in the mitochondrial membrane, releasing apoptogenic proteins like cytochrome ...
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Proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 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 peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid ...
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Ubiquitin Ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. In simple and more general terms, the ligase enables movement of ubiquitin from a ubiquitin carrier to another protein (the substrate) by some mechanism. The ubiquitin, once it reaches its destination, ends up being attached by an isopeptide bond to a lysine residue, which is part of the target protein. E3 ligases interact with both the target protein and the E2 enzyme, and so impart substrate specificity to the E2. Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. However, many other types of linkages are possible and alter a protein's activity, interactions, or localization. Ubiquitination by E3 ligases re ...
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Oncolytic Adenovirus
Adenovirus varieties have been explored extensively as a viral vector for gene therapy and also as an oncolytic virus. Of the many different viruses being explored for oncolytic potential, an adenovirus was the first to be approved by a regulatory agency, the genetically modified H101 strain. It gained regulatory approval in 2005 from China's State Food and Drug Administration (SFDA) for the treatment of head and neck cancer. Engineering of oncolytic adenovirus Adenoviruses have so far been through three generations of development. Some of the strategies for modification of adenoviruses are described below. Attenuation For adenovirus replication to occur, the host cell must be induced into S phase by viral proteins interfering with cell cycle proteins. The adenoviral E1A gene is responsible for inactivation of several proteins, including retinoblastoma, allowing entry into S-phase. The adenovirus E1B55kDa gene cooperates with another adenoviral product, E4ORF6, to inactivate p ...
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Atadenovirus
''Barthadenovirus'' is a genus of viruses, in the family ''Adenoviridae Adenoviruses (members of the family (biology), family ''Adenoviridae'') are medium-sized (90–100 nanometer, nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. ...''. Vertebrates serve as natural hosts. There are 21 species in this genus. From 2002 to 2024, the genus was named ''Atadenovirus''. Taxonomy The genus contains the following species, listed by scientific name and followed by the exemplar virus of the species: * ''Barthadenovirus amazonae'', Psittacine adenovirus 3 * ''Barthadenovirus bosquartum'', Bovine adenovirus 4 * ''Barthadenovirus bosseptimum'', Bovine adenovirus 7 * ''Barthadenovirus bossextum'', Bovine adenovirus 6 * ''Barthadenovirus caerulei'', Psittacine adenovirus 11 * ''Barthadenovirus cervi'', Deer adenovirus 1, also called Odocoileus adenovirus 1 * ''Barthadenovirus draconis'', Bearded ...
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Exaptation
Exaptation or co-option is a shift in the function of a trait during evolution. For example, a trait can evolve because it served one particular function, but subsequently it may come to serve another. Exaptations are common in both anatomy and behaviour. Bird feathers are a classic example. Initially they may have evolved for temperature regulation, but later were adapted for flight. When feathers were first used to aid in flight, that was an exaptive use. They have since then been shaped by natural selection to improve flight, so in their current state they are best regarded as adaptations for flight. So it is with many structures that initially took on a function as an exaptation: once molded for a new function, they become further adapted for that function. Interest in exaptation relates to both the process and products of evolution: the process that creates complex traits and the products (functions, anatomical structures, biochemicals, etc.) that may be imperfectly developed ...
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Mastadenovirus
''Mastadenovirus'' is a genus of viruses in the family ''Adenoviridae''. Humans and other mammals serve as natural hosts. There are 63 species in this genus. The genus as a whole includes many very common causes of human infection, estimated to be responsible for 2 to 5% of all respiratory infections, as well as gastrointestinal and eye infections. Symptoms are usually mild. Canine adenovirus 1 (CAdV-1) can lead to death in puppies, or encephalitis in other carnivore species. Etymology The name ''Mastadenovirus'' is derived from the Greek word ''mastos'' 'breast' (hence ''mammal'') and ''adenovirus'', named for the human adenoids, which the virus was first isolated from. Human serotypes Structure Viruses in ''Mastadenovirus'' are non-enveloped, with icosahedral geometries, and T=25 symmetry. The diameter is around 90 nm. Genomes are linear and non-segmented, around 35-36kb in length. The genome codes for 40 proteins. Life cycle Viral replication is nuclear. Entry i ...
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Concatemer
A concatemer is a long continuous DNA molecule that contains multiple copies of the same DNA sequence linked in series. These polymeric molecules are usually copies of an entire genome linked end to end and separated by ''cos'' sites (a protein binding nucleotide sequence that occurs once in each copy of the genome). Concatemers are frequently the result of rolling circle replication, and may be seen in the late stage of infection of bacteria by phages. As an example, if the genes in the phage DNA are arranged ABC, then in a concatemer the genes would be ABCABCABCABC and so on (assuming synthesis was initiated between genes C and A). They are further broken by ribozymes. During active infection, some species of viruses have been shown to replicate their genetic material via the formation of concatemers. In the case of ''human herpesvirus-6'', its entire genome is made over and over on a single strand. These long concatemers are subsequently cleaved between the pac-1 and pac-2 regio ...
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MRN Complex
The MRN complex (MRX complex in yeast) is a protein complex consisting of Mre11, Rad50 and Nbs1 (also known as Nibrin in humans and as Xrs2 in yeast). In eukaryotes, the MRN/X complex plays an important role in the initial processing of double-strand DNA breaks prior to repair by homologous recombination or non-homologous end joining. The MRN complex binds avidly to double-strand breaks both in vitro and in vivo and may serve to tether broken ends prior to repair by non-homologous end joining or to initiate DNA end resection prior to repair by homologous recombination. The MRN complex also participates in activating the checkpoint kinase ATM in response to DNA damage. Production of short single-strand oligonucleotides by Mre11 endonuclease activity has been implicated in ATM activation by the MRN complex. Evolutionary ancestry and biologic function The MRN complex has been mainly studied in eukaryotes. However, recent work shows that two of the three protein components o ...
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Caspase-3
Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the ''CASP3'' gene. ''CASP3'' orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. The CASP3 protein is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. Alternative splicing of this ...
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Transcription (genetics)
Transcription is the process of copying a segment of DNA into RNA for the purpose of gene expression. Some segments of DNA are transcribed into RNA molecules that can encode proteins, called messenger RNA (mRNA). Other segments of DNA are transcribed into RNA molecules called non-coding RNAs (ncRNAs). Both DNA and RNA are nucleic acids, which use base pairs of nucleotides as a complementary language. During transcription, a DNA sequence is read by an RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript. In virology, the term transcription is used when referring to mRNA synthesis from a viral RNA molecule. The genome of many RNA viruses is composed of negative-sense RNA which acts as a template for positive sense viral messenger RNA - a necessary step in the synthesis of viral proteins needed for viral replication. This process is catalyzed by a viral RNA dependent RNA polymerase. Background A DNA transcription unit encoding ...
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Caspase-9
Caspase-9 is an enzyme that in humans is encoded by the ''CASP9'' gene. It is an initiator caspase, critical to the apoptotic pathway found in many tissues. Caspase-9 homologs have been identified in all mammals for which they are known to exist, such as ''Mus musculus'' and ''Pan troglodytes''. Caspase-9 belongs to a family of caspases, cysteine-aspartic proteases involved in apoptosis and cytokine signalling. Apoptotic signals cause the release of cytochrome c from mitochondria and activation of apaf-1 ( apoptosome), which then cleaves the pro-enzyme of caspase-9 into the active dimer form. Regulation of this enzyme occurs through phosphorylation by an allosteric inhibitor, inhibiting dimerization and inducing a conformational change. Correct caspase-9 function is required for apoptosis, leading to the normal development of the central nervous system. Caspase-9 has multiple additional cellular functions that are independent of its role in apoptosis. Nonapoptotic roles of ...
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