Target type: biologicalprocess
Any process involving iron that activates or increases the rate of translational initiation. [GOC:go_curators]
Iron is an essential cofactor for numerous proteins involved in fundamental cellular processes, including DNA synthesis, respiration, and translation. The availability of iron can significantly influence the rate of protein synthesis, with iron deficiency leading to a decrease in protein synthesis and iron overload causing a disruption in cellular homeostasis. The positive regulation of translational initiation by iron involves a complex interplay of molecular players, including the iron-responsive element (IRE), iron regulatory proteins (IRP1 and IRP2), and the eukaryotic initiation factor 4E (eIF4E).
IREs are specific RNA sequences found in the 5' untranslated region (UTR) of mRNAs encoding proteins involved in iron metabolism. These IREs act as binding sites for IRPs, which are cytoplasmic proteins that sense cellular iron levels. When cellular iron levels are low, IRPs bind to IREs with high affinity. This binding event can either block the translation of mRNAs containing IREs in their 5' UTR or stabilize the mRNAs containing IREs in their 3' UTR.
In the case of mRNAs encoding proteins involved in iron uptake, such as the transferrin receptor (TfR), the binding of IRPs to the IREs in their 5' UTRs inhibits their translation. This prevents the synthesis of proteins that increase iron uptake when iron levels are already low. Conversely, in the case of mRNAs encoding proteins involved in iron storage, such as ferritin, the binding of IRPs to the IREs in their 5' UTRs stabilizes these mRNAs, preventing their degradation. This ensures that the mRNAs encoding iron storage proteins are available for translation when iron levels increase, allowing for the storage of excess iron.
When cellular iron levels are high, iron binds to IRPs, causing a conformational change that reduces their affinity for IREs. This allows the translation of mRNAs encoding iron uptake proteins, increasing iron uptake. It also destabilizes the mRNAs encoding iron storage proteins, reducing their translation. This ensures that iron levels remain within a narrow range that is optimal for cellular function.
eIF4E is a key regulator of translation initiation. It binds to the 5' cap structure of mRNAs, promoting their recruitment to ribosomes. Iron can positively regulate translation initiation by influencing the activity of eIF4E. In some cases, iron can promote the binding of eIF4E to mRNAs, thereby enhancing translation initiation. The exact mechanism by which iron influences eIF4E activity is still under investigation but may involve iron-dependent phosphorylation events or the interaction of iron with specific regulatory proteins that control eIF4E activity.
In summary, positive regulation of translational initiation by iron is a complex process that involves the interplay of multiple factors, including iron-responsive elements (IREs), iron regulatory proteins (IRPs), and the eukaryotic initiation factor 4E (eIF4E). This regulatory mechanism ensures that the synthesis of proteins involved in iron metabolism is tightly controlled in response to changes in cellular iron levels, allowing for the efficient utilization of iron for essential cellular processes.'
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Protein | Definition | Taxonomy |
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Tumor necrosis factor | A tumor necrosis factor that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
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mesalamine | mesalamine : A monohydroxybenzoic acid that is salicylic acid substituted by an amino group at the 5-position. Mesalamine: An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed) | amino acid; aromatic amine; monocarboxylic acid; monohydroxybenzoic acid; phenols | non-steroidal anti-inflammatory drug |
way 151693 | |||
pentoxifylline | oxopurine | ||
4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone | 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone: Inhibitor of phosphodiesterases. | methoxybenzenes | |
rolipram | pyrrolidin-2-ones | antidepressant; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor | |
sulfasalazine | sulfasalazine : An azobenzene consisting of diphenyldiazene having a carboxy substituent at the 4-position, a hydroxy substituent at the 3-position and a 2-pyridylaminosulphonyl substituent at the 4'-position. Sulfasalazine: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907) | ||
bergenin | bergenin: RN refers to (2R-(2alpha,3beta,4alpha,4aalpha,10bbeta))-isomer; structure | trihydroxybenzoic acid | metabolite |
marimastat | marimastat : A secondary carboxamide resulting from the foraml condensation of the carboxy group of (2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoic acid with the alpha-amino group of N,3-dimethyl-L-valinamide. marimastat: a matrix metalloproteinase inhibitor active in patients with advanced carcinoma of the pancreas, prostate, or ovary | hydroxamic acid; secondary carboxamide | antineoplastic agent; matrix metalloproteinase inhibitor |
birb 796 | aromatic ether; morpholines; naphthalenes; pyrazoles; ureas | EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor; immunomodulator | |
ganoderic acid a | triterpenoid | ||
ganoderiol f | ganoderiol F: a ganoderma triterpene from Ganoderma amboinense; structure in first source | triterpenoid | |
1-(phenylmethyl)benzimidazole | benzimidazoles | ||
luteolin-7-glucoside | luteolin 7-O-beta-D-glucoside : A glycosyloxyflavone that is luteolin substituted by a beta-D-glucopyranosyl moiety at position 7 via a glycosidic linkage. luteolin-7-glucoside: has both antiasthmatic and antineoplastic activities; has 3C protease inhibitory activity; isolated from Ligustrum lucidum | beta-D-glucoside; glycosyloxyflavone; monosaccharide derivative; trihydroxyflavone | antioxidant; plant metabolite |
apigetrin | apigenin 7-O-beta-D-glucoside : A glycosyloxyflavone that is apigenin substituted by a beta-D-glucopyranosyl moiety at position 7 via a glycosidic linkage. apigetrin: structure given in first source | beta-D-glucoside; dihydroxyflavone; glycosyloxyflavone; monosaccharide derivative | antibacterial agent; metabolite; non-steroidal anti-inflammatory drug |
calycosin-7-o-beta-d-glucopyranoside | calycosin-7-O-beta-D-glucoside : A glycosyloxyisoflavone that is calycosin substituted by a beta-D-glucopyranosyl residue at position at 7 via a glycosidic linkage. calycosin-7-O-beta-D-glucoside: from Radix Astragali | 4'-methoxyisoflavones; 7-hydroxyisoflavones 7-O-beta-D-glucoside; hydroxyisoflavone; monosaccharide derivative | |
spd-304 | SPD-304: structure in first source | ||
ganoderic acid f | ganoderic acid F: isolated from Ganoderma lucidum; structure in first source | triterpenoid | |
ganoderic acid c2 | ganoderic acid C2: from the fruiting body of Ganoderma; structure in first source | triterpenoid |