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Chaperone-assisted Selective Autophagy
Chaperone-assisted selective autophagy is a cellular process for the selective, ubiquitin-dependent degradation of chaperone-bound proteins in lysosomes. Autophagy (Greek: ‘self-eating’) was initially identified as a catabolic process for the unselective degradation of cellular content in lysosomes under starvation conditions. However, autophagy also comprises selective degradation pathways, which depend on ubiquitin conjugation to initiate sorting to lysosomes. In the case of chaperone-assisted selective autophagy, dysfunctional, nonnative proteins are recognized by molecular chaperones and become ubiquitinated by chaperone-associated ubiquitin ligases. The ubiquitinated proteins are enclosed in autophagosomes, which eventually fuse with lysosomes, leading to the degradation of the dysfunctional proteins. Chaperone-assisted selective autophagy is a vital part of the cellular protein quality control system. It is essential for protein homeostasis (proteostasis) in neurons and i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A. The addition of ubiquitin to a substrate protein is called ubiquitylation (or, alternatively, ubiquitination or ubiquitinylation). Ubiquitylation affects proteins in many ways: it can mark them for degradation via the proteasome, alter their cellular location, affect their activity, and promote or prevent protein interactions. Ubiquitylation involves three main steps: activation, conjugation, and ligation, performed by ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s), respectively. The result of this sequential cascade is to bind ubiquitin to lysine residues on the protein substrate via an isopeptide bond, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
STUB1
STUB1 (STIP1 homology and U-Box containing protein 1) is a human gene that codes for the protein CHIP (C terminus of HSC70-Interacting Protein). Function The CHIP protein encoded by this gene binds to and inhibits the ATPase activity of the chaperone (protein), chaperone proteins HSPA8, HSC70 and Hsp70, HSP70 and blocks the forward reaction of the HSC70-HSP70 substrate-binding cycle. In addition, CHIP possesses ubiquitin ligase, E3 ubiquitin ligase activity and promotes ubiquitylation, mainly of chaperone-bound misfolded proteins. CHIP enhances HSP70 induction during acute stress and also mediates its turnover during the stress recovery process. Hence CHIP appears to maintain protein homeostasis by controlling chaperone levels during stress and recovery. Mutations in STUB1 cause spinocerebellarataxiatype 16. Interactions STUB1 has been shown to Protein-protein interaction, interact with: * C-Raf, * DNAJB1, * HSPA1A, * HSPA4, * HSPA8, * Parkin (ligase), and * RUNX2. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Muscle Dystrophy
Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin. Some types are also associated with problems in other organs. Over 30 different disorders are classified as muscular dystrophies. Of those, Duchenne muscular dystrophy (DMD) accounts for approximately 50% of cases and affects males beginning around the age of four. Other relatively common muscular dystrophies include Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy, whereas limb–girdle muscular dystrophy and congenital muscular dystrophy are themselves groups of several – usually ultrarare – genetic disorders. Muscular dystrophies are caused by mutations in genes, usually those involved in making muscle proteins. T ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Filamin
Filamins are a class of proteins that hold two actin filaments at large angles. Filamin protein in mammals is made up of an actin-binding domain at its N-terminus that is followed by 24 immunoglobulin-like repeat modules of roughly 95 amino acids. There are two hinge regions; between repeats 15-16 and 23-24. Filamin gets cleaved at these hinge regions to generate smaller fragments of the protein. Filamin has two actin-binding sites with a V-linkage between them, so that it cross-links actin filaments into a network with the filaments orientated almost at right angles to one another. Filamin proteins include: * FLNA * FLNB * FLNC Over-expression of FLNA stops the regeneration of bladder carcinoma (BC) cells, by inhibiting the cell cycle and inducing apoptosis of BC cells. FLNA has also been shown to reduce the mobility Mobility may refer to: Social sciences and humanities * Economic mobility, ability of individuals or families to improve their economic status * Geographic mobi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over 100 μM; its mass is roughly 42 kDa, with a diameter of 4 to 7 nm. An actin protein is the monomeric subunit of two types of filaments in cells: microfilaments, one of the three major components of the cytoskeleton, and thin filaments, part of the contractile apparatus in muscle cells. It can be present as either a free monomer called G-actin (globular) or as part of a linear polymer microfilament called F-actin (filamentous), both of which are essential for such important cellular functions as the mobility and contraction of cells during cell division. Actin participates in many important cellular processes, including muscle contraction, cell motility, cell division and cytokinesis, vesicle and organelle movement, cell sign ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Huntington's Disease
Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unsteady gait often follow. It is also a basal ganglia disease causing a hyperkinetic movement disorder known as chorea. As the disease advances, uncoordinated, involuntary body movements of chorea become more apparent. Physical abilities gradually worsen until coordinated movement becomes difficult and the person is unable to talk. Mental abilities generally decline into dementia. The specific symptoms vary somewhat between people. Symptoms usually begin between 30 and 50 years of age but can start at any age. The disease may develop earlier in each successive generation. About eight percent of cases start before the age of 20 years, and are known as ''juvenile HD'', which typically present with the slow movement symptoms of Parkinson's d ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Huntingtin
Huntingtin (Htt) is the protein coded for in humans by the ''HTT'' gene, also known as the ''IT15'' ("interesting transcript 15") gene. Mutated ''HTT'' is the cause of Huntington's disease (HD), and has been investigated for this role and also for its involvement in long-term memory storage. It is variable in its structure, as the many polymorphisms of the gene can lead to variable numbers of glutamine residues present in the protein. In its wild-type (normal form), it contains 6-35 glutamine residues. However, in individuals affected by Huntington's disease (an autosomal dominant genetic disorder), it contains more than 36 glutamine residues (highest reported repeat length is about 250). Its commonly used name is derived from this disease; previously, the ''IT15'' label was commonly used. The mass of huntingtin protein is dependent largely on the number of glutamine residues it has; the predicted mass is around 350 kDa. Normal huntingtin is generally accepted to be 3144 am ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
VPS18
Vacuolar protein sorting-associated protein 18 homolog is a protein that in humans is encoded by the ''VPS18'' gene. Function Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps18 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. Interactions VPS18 has been shown to interact with VPS11 and STX7 Syntaxin-7 is a protein that in humans is encoded by the ''STX7'' gene. In melanocytic cells STX7 gene expression may be regulated by MITF. Interactions STX7 has been shown to interact with STX8, VPS18, Vesicle-associated membrane protein 8 .... References ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SYNPO2
Myopodin protein, also called Synaptopodin-2 is a protein that in humans is encoded by the ''SYNPO2'' gene. Myopodin is expressed in cardiac, smooth muscle and skeletal muscle, and localizes to Z-disc structures. Structure Myopodin is a 117.4 kDa protein composed of 1093 amino acids, although four alternatively-spliced isoforms have been described. Myopodin contains one PPXY motif, multiple PXXP motifs, and two potential nuclear localization sequences (one N-terminal and one C-terminal). PPXY motifs have been shown to mediate interactions, and PXXP motifs represent potential sites of interaction for SH3 domain-containing proteins. Myopodin contains a novel actin binding site (between amino acids 410 and 563) in the center of the protein. Function During myotube differentiation, myopodin interacts with stress fibers prior to co-localizing with alpha actinin-2 at Z-discs in mature striated muscle cells. Myopodin has been shown to shuttle between the nucleus and cytoplasm in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SQSTM1
Sequestosome-1 is a protein that in humans is encoded by the ''SQSTM1'' gene. Also known as the ubiquitin-binding protein p62, it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy. By interacting with GATA4 and targeting it for degradation, it can inhibit GATA-4 associated senescence and senescence-associated secretory phenotype. Model organisms Model organisms have been used in the study of SQSTM1 function. A conditional knockout mouse line, called ''Sqstm1tm1a(KOMP)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out on homozygous mutant mice and one significant abnormality was observed: females had abnormal complete blood count paramete ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ubiquitination
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A. The addition of ubiquitin to a substrate protein is called ubiquitylation (or, alternatively, ubiquitination or ubiquitinylation). Ubiquitylation affects proteins in many ways: it can mark them for degradation via the proteasome, alter their cellular location, affect their activity, and promote or prevent protein interactions. Ubiquitylation involves three main steps: activation, conjugation, and ligation, performed by ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s), respectively. The result of this sequential cascade is to bind ubiquitin to lysine residues on the protein substrate via an isopeptide bond, cy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BAG3
BAG family molecular chaperone regulator 3 is a protein that in humans is encoded by the ''BAG3'' gene. BAG3 is involved in chaperone-assisted selective autophagy. Function BAG proteins compete with Hip-1 for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The protein encoded by this gene contains a WW domain in the N-terminal region and a BAG domain in the C-terminal region. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain ''in vitro'' and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. Clinical significance BAG gene has been implicated in age related neurodegenerative diseases such as Alzheimer's. It has been demonstrated that BAG1 and BAG3 regulate the proteasomal an ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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