Publications by authors named "K O Shostak"
Article Synopsis
- Researchers discovered a specific motif (YDDΦxΦ) in NF-κB pathway substrates that helps these substrates dock with IKK dimers, showing a link between how well they bind and IKK activity, particularly in IκBα phosphorylation and degradation.
- The study suggests that a certain phosphorylation event on this motif reduces its ability to dock with IKK, which can influence NF-κB signaling, and also indicates that disrupting IKK dimerization disrupts substrate binding.
Intestinal tuft cells are critical for anti-helminth parasite immunity because they produce IL-25, which triggers IL-13 secretion by activated group 2 innate lymphoid cells (ILC2s) to expand both goblet and tuft cells. We show that epithelial Elp3, a tRNA-modifying enzyme, promotes tuft cell differentiation and is consequently critical for IL-25 production, ILC2 activation, goblet cell expansion and control of Nippostrongylus brasiliensis helminth infection in mice. Elp3 is essential for the generation of intestinal immature tuft cells and for the IL-13-dependent induction of glycolytic enzymes such as Hexokinase 1 and Aldolase A.
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- Transfer RNA (tRNA) dynamics play a significant role in cancer by influencing how messenger RNA (mRNA) translates into proteins, specifically through aminoacyl-tRNA synthetases that can either encourage or inhibit tumor growth.
- Research indicates that valine aminoacyl-tRNA synthetase (VARS) is crucial for the changes in protein translation related to resistance against MAPK therapy in melanoma patients, as there is an increased use of valine in their proteomes.
- Additionally, reducing VARS levels can make MAPK-resistant melanoma cells more sensitive to treatment, as VARS is linked to the translation of key mRNAs that support cell survival via fatty acid oxidation.
Genetic studies have shown that the MAP kinase MGV1 and the transcriptional regulator TRI6 regulate many of the same biosynthetic gene clusters (BGCs) in . This study sought to investigate the relationship between and in the regulatory hierarchy. Transgenic strains constitutively expressing and were generated to address both independent and epistatic regulation of BGCs by and .
View Article and Find Full Text PDFMacrophage polarization is a process whereby macrophages acquire distinct effector states (M1 or M2) to carry out multiple and sometimes opposite functions. We show here that translational reprogramming occurs during macrophage polarization and that this relies on the Elongator complex subunit Elp3, an enzyme that modifies the wobble uridine base U34 in cytosolic tRNAs. Elp3 expression is downregulated by classical M1-activating signals in myeloid cells, where it limits the production of pro-inflammatory cytokines via FoxO1 phosphorylation, and attenuates experimental colitis in mice.
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