Yeast two-hybrid assay results indicated that MKT1 directly interacts with EIF4G5. MKT1-PBP1 complexes can therefore interact with mRNAs via their poly(A) tails and caps, as well as through sequence-specific RNA-binding proteins. Correspondingly, MKT1 is associated with many mRNAs, although not with those encoding ribosomal proteins. Meanwhile, MKT1L resembles MKT1 at the C-terminus, but additionally features an N-terminal extension with low-complexity regions. Although MKT1L depletion inhibited cell proliferation, we found no evidence that it specifically interacts with RNA-binding proteins or mRNA. We speculate that MKT1L may compete with MKT1 for PBP1 binding and thereby modulate the function of MKT1-containing complexes.Mediator complex subunit 16 (MED16) is a component of the mediator complex and functions as a coactivator in transcriptional events at almost all RNA polymerase II-dependent genes. In this study, we report that the expression of MED16 is markedly decreased in papillary thyroid cancer (PTC) tumors compared with normal thyroid tissues. In vitro, MED16 overexpression in PTC cells significantly inhibited cell migration, enhanced sodium/iodide symporter (NIS) expression and iodine uptake, and decreased resistance to radioactive 131I (RAI). Conversely, PTC cells in which MED16 had been further knocked down (MED16KD) exhibited enhanced cell migration, epithelial-mesenchymal transition (EMT), and RAI resistance, accompanied by decreased sodium/iodide symporter (NIS) levels. Moreover, cell signaling through transforming growth factor β (TGF-β) was highly activated after the MED16 knockdown. Similar results were obtained in MED12KD PTC cells, and a co-immunoprecipitation experiment verified interactions between MED16 and MED12 and MED16 and TGF-βR2. Of note, the application of LY2157299, a potent inhibitor of TGF-β signaling, significantly attenuated MED16KD-induced RAI resistance both in vitro and in vivo. In conclusion, our findings indicate that MED16 reduction in PTC contributes to tumor progression and RAI resistance via the activation of the TGF-β pathway.The single von Willebrand factor C-domain proteins (SVWCs) are mainly found in arthropods. Their expression may be regulated by several environmental stresses, including nutritional status and bacterial and viral infections. However, the underlying regulatory mechanism is unclear. In the present study, we identified a member of the SVWC family from the oriental river prawn Macrobrachium nipponense as a soluble and bacteria-inducible pattern-recognition receptor (designated MnSVWC). In vitro, recombinant MnSVWC exhibited pronounced binding and Ca2+-dependent agglutinating abilities against diverse microbes, including Gram-negative bacteria (i.e.  https://www.selleckchem.com/products/ly333531.html  Escherichia coli and Aeromonas victoria), Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), and yeast (Pichia pastoris). ELISA assays revealed that recombinant MnSVWC recognizes a broad range of various pathogen-associated molecular patterns (PAMPs), has high affinity to lipopolysaccharide and lysine-type and diaminopimelic acid-type peptidylglycan and D-galactose, and low affinity to D-mannan and β-1,3-glucan. Mutant MnSVWCP57A with an impaired Glu-Pro-Asn (EPN) motif displayed reduced affinity to all these PAMPs to varying extent. Moreover, MnSVWC bound to the surface of hemocytes and promoted their phagocytic activity and clearance of invasive bacteria. RNAi-mediated MnSVWC knockdown in prawn reduced the ability to clear invading bacteria, but did not block the activities of the Toll pathway or the arthropod immune deficiency (IMD) pathway, or the expression of antimicrobial peptide genes. These results indicate that MnSVWC functions as an extracellular pattern-recognition receptor in M. nipponense that mediates cellular immune responses by recognizing PAMPs, agglutinating invasive microbes, and promoting phagocytosis in hemocytes.AhpC is a bacterial representative of 2-Cys peroxiredoxins (Prxs) with broad substrate specificity and functional plasticity. However, details underpinning these two important attributes of AhpC remain unclear. Here, we studied the functions and mechanisms of regulation of AhpC in the facultative Gram-negative anaerobic bacterium Shewanella oneidensis, in which AhpC's physiological roles can be conveniently assessed through its suppression of a plating defect due to the genetic loss of a major catalase. We show that successful suppression can be achieved only when AhpC is produced in a dose- and time-dependent manner through a complex mechanism involving activation of the transcriptional regulator OxyR, transcription attenuation, and translation reduction. By analyzing AhpC truncation variants, we demonstrate that reactivity with organic peroxides (OPs) rather than H2O2 is resilient to mutagenesis, implying that OP reduction is the core catalytic function of AhpC. Intact AhpC could be recycled only by its cognate reductase AhpF, and AhpC variants lacking the Prx domain or the extreme C-terminal five residues became promiscuous electron acceptors from the thioredoxin reductase TrxR and the glutathione reductase Gor in addition to AhpF, implicating an additional dimension to functional plasticity of AhpC. Finally, we show that the activity of S. oneidensis AhpC is less affected by mutations than that of its Escherichia coli counterpart. These findings suggest that the physiological roles of bacterial AhpCs are adapted to different oxidative challenges, depending on the organism, and that its functional plasticity is even more extensive than previously reported.T cell-mediated immunity is governed primarily by T cell receptor (TCR) recognition of peptide human leukocyte antigen complexes (pHLA) and is essential for immunosurveillance and disease control. This interaction is generally stabilised by interactions between the HLA surface and TCR germline encoded complementarity determining region (CDR) loops 1 and 2, whereas peptide selectivity is guided by direct interactions with the TCR CDR3 loops. Here, we solved the structure of a newly identified TCR in complex with a clinically relevant peptide derived from the cancer testis antigen melanoma antiGEn-A4 (MAGE-A4). The TCR bound pHLA in a position shifted toward the peptide's N-terminus. This enabled the TCR to achieve peptide selectivity via an indirect mechanism, whereby the TCR sensed the first residue of the peptide through HLA residue Trp167, which acted as a tuneable gateway. Amino acid substitutions at peptide position 1 predicted to alter the HLA Trp167 sidechain conformation abrogated TCR binding, indicating that this indirect binding mechanism is essential for peptide recognition.