Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of the directed movement of substances between the nucleus and the cytoplasm. [GOC:bf]
Nucleocytoplasmic transport is a highly regulated process that governs the movement of molecules between the nucleus and cytoplasm of eukaryotic cells. It is essential for maintaining cellular homeostasis and orchestrating a wide range of cellular functions, including gene expression, DNA replication, and cell signaling. This intricate process is tightly controlled by a complex machinery of nuclear transport receptors, chaperones, and nuclear pore complexes (NPCs), which act in concert to ensure the selective and efficient transport of cargo molecules across the nuclear envelope.
The nuclear envelope, a double-membrane structure that encloses the nucleus, serves as the barrier between the nuclear and cytoplasmic compartments. The NPCs, embedded within the nuclear envelope, act as the sole gateways for nucleocytoplasmic transport. These elaborate protein complexes are composed of numerous proteins known as nucleoporins, which form a selective barrier that allows for the passage of specific molecules while restricting the movement of others.
The transport of molecules across the NPCs is facilitated by nuclear transport receptors, also known as importins and exportins. These receptors bind to specific cargo molecules and escort them through the NPCs. The interaction between transport receptors and their cargo is regulated by the presence of nuclear localization signals (NLSs) and nuclear export signals (NESs), short amino acid sequences that serve as targeting signals for nuclear import and export, respectively.
Importins, responsible for nuclear import, bind to cargo molecules containing NLSs and guide them into the nucleus. Conversely, exportins bind to cargo molecules containing NESs and facilitate their export from the nucleus to the cytoplasm. The movement of transport receptors and their cargo through the NPCs is driven by a combination of factors, including GTP hydrolysis, protein-protein interactions, and concentration gradients.
The process of nuclear import is initiated when an importin binds to a cargo molecule containing an NLS. This complex then interacts with the NPC, specifically with the FG-repeat domain of nucleoporins. These repetitive amino acid sequences create a mesh-like structure within the NPC that acts as a selective barrier. The movement of the importin-cargo complex through the NPC is facilitated by the GTPase Ran, a small GTP-binding protein that is localized to the nucleus. Ran in its GTP-bound form interacts with importins, promoting the release of the cargo within the nucleus.
The export of molecules from the nucleus follows a similar mechanism. Exportins bind to cargo molecules containing NESs and interact with the NPC. The movement of the exportin-cargo complex through the NPC is facilitated by Ran in its GDP-bound form, which promotes the release of the cargo within the cytoplasm.
Regulation of nucleocytoplasmic transport is essential for maintaining cellular homeostasis and ensuring proper cellular function. This intricate process is subject to various regulatory mechanisms, including post-translational modifications, protein-protein interactions, and signaling pathways. Disruptions in nucleocytoplasmic transport can lead to various cellular dysfunctions and have been implicated in the pathogenesis of several diseases, including cancer, neurodegenerative disorders, and infectious diseases.
In summary, nucleocytoplasmic transport is a highly regulated and essential process that governs the movement of molecules between the nucleus and cytoplasm. This intricate process is orchestrated by a complex machinery of nuclear transport receptors, chaperones, and NPCs, which work together to ensure the selective and efficient transport of cargo molecules across the nuclear envelope. Disruptions in nucleocytoplasmic transport can have profound implications for cellular function and disease pathogenesis. '
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Protein | Definition | Taxonomy |
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Serine/threonine-protein phosphatase PP1-gamma catalytic subunit | A serine/threonine-protein phosphatase PP1-gamma catalytic subunit that is encoded in the genome of human. [PRO:DNx, UniProtKB:P36873] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
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cantharidin | cantharidin : A monoterpenoid with an epoxy-bridged cyclic dicarboxylic anhydride structure secreted by many species of blister beetle, and most notably by the Spanish fly, Lytta vesicatoria. Natural toxin inhibitor of protein phosphatases 1 and 2A. Cantharidin: A toxic compound, isolated from the Spanish fly or blistering beetle (Lytta (Cantharis) vesicatoria) and other insects. It is a potent and specific inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A). This compound can produce severe skin inflammation, and is extremely toxic if ingested orally. | cyclic dicarboxylic anhydride; monoterpenoid | EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor; herbicide |
cyanoginosin lr | cyanoginosin LR: cyclic heptapeptide from cyanobacterium Microcystis aeruginosa microcystin-LR : A microcystin consisting of D-alanyl, L-leucyl, (3S)-3-methyl-D-beta-aspartyl,L-arginyl, 2S,3S,4E,6E,8S,9S)-3-amino-4,5,6,7-tetradehydro-9-methoxy-2,6,8-trimethyl-10-phenyldecanoyl, D-gamma-glutamyl, and 2,3-didehydro-N-methylalanyl residues joined into a 25-membered macrocycle. Produced by the cyanobacterium Microcystis aeruginosa, it is the most studied of the microcystins. | microcystin | bacterial metabolite; EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor; environmental contaminant; xenobiotic |
okadaic acid | polycyclic ether | calcium ionophore; EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor; marine metabolite | |
calyculin a | calyculin A: RN given refers to (5S-(5alpha(2R*(1S*,3S*,4S*,5R*,6R*,7E,9E,11E,13Z),3R*),7beta(E(S*)),*beta,9alpha))-isomer |