Stress granules are aggregates of small ribosomal subunits, mRNA, and numerous associated RNA-binding proteins that include several translation initiation factors. granule assembly occurs in the cytoplasm higher eukaryotic cells under a wide variety stress conditions, including heat shock, UV irradiation, hypoxia, exposure to arsenite. Thus far, unifying principle factor 2alpha phosphorylation prior formation has been observed from majority experimental evidence. Pateamine A, natural product...

Nonsense-mediated mRNA decay (NMD) in mammalian cells is a key mechanism for the removal of containing premature stop codons and mediated by coordinated function numerous proteins that dynamically associate with exon junction complex. The information communicated these interactions functional consequences from mechanistic perspective, however, are not completely documented. Herein, we report natural product pateamine A (PatA) capable inhibiting NMD through direct interaction eIF4AIII, which...

A cDNA clone encoding a presumptive antifreeze protein was isolated from skin library shorthorn sculpin, Myoxocephalus scorpius. The encodes 92-residue mature polypeptide (sssAFP-2) without any signal and prosequence, which suggests an intracellular localization. It is the largest alanine-rich, α-helical type I known. recombinant fusion containing N-terminal-linked His-tag produced purified Escherichia coli. This at 0 °C exhibits significant activity. Northern blot reverse...

The antifreeze polypeptides (AFPs) are found in several marine fish and have been grouped into four distinct biochemical classes (type I-IV). Recently, the new subclass of skin-type, type I AFPs that produced intracellularly as mature identified winter flounder (Pleuronectes americanus) shorthorn sculpin (Myoxocephalus scorpius). This study demonstrates presence skin-type longhorn octodecemspinosus), which produces IV serum AFPs. Using polymerase chain reaction-based methods, a clone encoded...

The natural product pateamineA (PatA) is a highly potent antiproliferative agent. PatA and the simplified analog desmethyl, desamino (DMDAPatA) have exhibited cytotoxicity selective for rapidly proliferating cells, been shown to inhibit cap-dependent translation initiation through binding eIF4A (eukaryotic factor 4A) of eIF4F complex. DMDAPatA are both known stimulate RNA-dependent ATPase, ATP-dependent RNA helicase activities eIF4A. impact other components, eIF4E eIF4G, on action were...

The synthesis and characterization of thermoresponsive, water-soluble poly-N-isopropyl acrylamide (PNIPAM) derived macroligands displaying cyclosporin A (CsA) dexamethasone (Dex) for use as novel affinity resins are described. Characterization these soluble macroligands, including ligand loading integrity, was determined by 1H NMR spectroscopy. One the CsA used in a protein experiment to capture known binding proteins CsA, cyclophilins, from Jurkat T-cell lysates.

Antifreeze proteins (AFPs) are found in many marine fish and have been classified into five biochemical classes: AFP types I-IV the antifreeze glycoproteins. Type I AFPs alpha-helical, partially amphipathic, Ala-rich polypeptides. The winter flounder (Pleuronectes americanus) produces two type subclasses, liver-type (wflAFPs) skin-type (wfsAFPs), that encoded by distinct gene families with different tissue-specific expression. wfsAFPs wflAFPs share a high level of identity even though...

The marine natural product PateamineA (PatA) and the simplified analog desmethyl, desamino (DMDAPatA) have cytotoxicity selective for rapidly proliferating cells by inhibition of cap‐dependent translation initiation through binding to eIF4A (eukaryotic factor 4A). is a member eIF4F which includes eIF4E (cap‐binding protein) eIF4G (scaffolding protein). DEAD‐box helicase that unwinds secondary structure in 5ʹ‐untranslated region (5ʹ‐UTR) mRNA allowing recruitment 43S pre‐initiation complex...

The DExD-box family (DEAD-box) of proteins was surveyed for eukaryotic translation initiation factor 4A-specific sequences surrounding the DEAD box. An eIF4A-unique glutamate residue (E186 in eIF4AI) identified immediately following D-E-A-D sequence eIF4AI, II, and III that found to be conserved from yeast Man. Mutation a selection alternative amino acids performed within recombinant eIF4AI expressed Escherichia coli mutant were RNA-dependent ATPase activity. mutants also investigated...

The natural product Pateamine A (PatA) from the marine sponge Mycale hentscheli has been found to be a highly potent antiproliferative agent with potential as novel anti‐neoplastic agent. PatA binds eukaryotic translation initiation factor 4A (eIF4A) and prevents initiation. Previous structure/activity relationship (SAR) studies identified rigid binding region on molecule consisting of “eastern” portion macrolide ring side chain terminating in N,N‐dimethyl tertiary amine. “western” serves...

Natural products have served as a source for many modern therapeutics. Over the past decade, high throughput screening of libraries small molecule compounds been popular in drug discovery. One such natural product is PateamineA (PatA). The PatA isolated from marine sponge Mycale hentscheli has found to be highly potent antiproliferative agent with potential novel anti‐neoplastic agent. and simplified analog desmethyl, desamino (DMDAPatA) cytotoxicity selective rapidly proliferating cells by...

Translation initiation in eukaryotes is accomplished through the coordinated and orderly action of a large number proteins known as factors ribosomal subunits. Herein we report that pateamine A (PatA), potent antiproliferative proapoptotic marine natural product, inhibits cap-dependent eukaryotic translation initiation. Crucial to mechanism multisubunit factor eIF4F, which composed eIF4G, eIF4E, eIF4A factors. PatA bound enhanced intrinsic enzymatic activities eIF4A, yet it inhibited...

eIF4E‐binding proteins (eIF4E‐BPs or 4E‐BPs) are a family of that inhibit the initiation eukaryotic translation. They bind to eIF4E and formation eIF4F complex which is crucial for cap‐dependent translation initiation. There 3 isotypes 4E‐BPs, 4E‐BP1, 4E‐BP2 4E‐BP3. nearly 60% identical at amino acid level. According NCBI reference sequences, has long 3′ UTR (6.8kb) whereas 4E‐BP1 (428 bp) 4E‐BP3 (315 do not. The presence this relatively longer could indicate cis‐acting regulatory elements...

Many organisms are known to survive in icy environments. These include both over wintering terrestrial insects and plants as well the marine fish inhabiting high latitudes. The adaptation of these is a fascinating important topic biology. Marine teleosts particular, can encounter ice-laden seawater that approximately <TEX>$1^{\circ}C$</TEX> colder than colligative freezing point their body fluids. animals produce unique group proteins, antifreeze proteins (AFPs) or glycoproteins (AFGPs)...

eIF4E-binding proteins (4E-BPs) are a family of translational repressors, when unphosphorylated or hypo-phosphorylated, can bind to eIF4E and inhibit eukaryotic cap-dependent translation initiation. The 3 4E-BPs (4E-BP1, 4E-BP2 4E-BP3) not isoforms but often regarded alike in terms inhibiting They clearly differentiated function. Not only do they originate from different genes on chromosomes, also have distinct mRNA structure. We hypothesized potential for their differential regulation under...