The immunometabolite itaconate stimulates OXGR1 to promote mucociliary clearance during the pulmonary innate immune response.

Pathogens and inflammatory conditions rapidly induce the expression of immune-responsive gene 1 (IRG1) in cells of myeloid lineage. IRG1 encodes an aconitate decarboxylase (ACOD1) that produces the immunomodulatory metabolite itaconate (ITA). In addition to rapid intracellular accumulation, ITA is also secreted from the cell, but whether secreted ITA functions as a signaling molecule is unclear.

Itaconate inhibits TET DNA dioxygenases to dampen inflammatory responses.

As one of the most induced genes in activated macrophages, immune-responsive gene 1 (IRG1) encodes a mitochondrial metabolic enzyme catalysing the production of itaconic acid (ITA). Although ITA has an anti-inflammatory property, the underlying mechanisms are not fully understood. Here we show that ITA is a potent inhibitor of the TET-family DNA dioxygenases.

CK2 Down-Regulation Increases the Expression of Senescence-Associated Secretory Phenotype Factors through NF-κB Activation.

Senescent cells secrete pro-inflammatory factors, and a hallmark feature of senescence is senescence-associated secretory phenotype (SASP). The aim of this study is to investigate the protein kinase CK2 (CK2) effects on SASP factors expression in cellular senescence and organism aging. Here CK2 down-regulation induced the expression of SASP factors, including interleukin (IL)-1β, IL-6, and matrix metalloproteinase (MMP) 3, through the activation of nuclear factor-κB (NF-κB) signaling in MCF-7 and HCT116 cells.

The Zscan4-Tet2 Transcription Nexus Regulates Metabolic Rewiring and Enhances Proteostasis to Promote Reprogramming.

Evolutionarily conserved SCAN (named after SRE-ZBP, CTfin51, AW-1, and Number 18 cDNA)-domain-containing zinc finger transcription factors (ZSCAN) have been found in both mouse and human genomes. Zscan4 is transiently expressed during zygotic genome activation (ZGA) in preimplantation embryos and induced pluripotent stem cell (iPSC) reprogramming. However, little is known about the mechanism of Zscan4 underlying these processes of cell fate control.

Protein kinase CK2 activates Nrf2 via autophagic degradation of Keap1 and activation of AMPK in human cancer cells.

Protein kinase CK2 downregulation induces premature senescence in various human cell types via activation of the reactive oxygen species (ROS)-p53-p21 pathway. The transcription factor "nuclear factor erythroid 2-related factor 2" (Nrf2) plays an important role in maintaining intracellular redox homeostasis. In this study, Nrf2 overexpression attenuated CK2 downregulation- induced ROS production and senescence markers including SA-β-gal staining and activation of p53-p21 in human breast (MCF-7) and colon (HCT116) cancer cells.

CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases.

The ubiquitin proteasome pathway is one of the major regulatory tools used by eukaryotic cells. The evolutionarily conserved cullin family proteins can assemble as many as >600 distinct E3 ubiquitin ligase complexes that regulate diverse cellular pathways. In most of Cullin-RING ubiquitin ligase (CRL) complexes, separate linker and adaptor proteins build the substrate recognition module.

SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response.

The TET2 DNA dioxygenase regulates gene expression by catalyzing demethylation of 5-methylcytosine, thus epigenetically modulating the genome. TET2 does not contain a sequence-specific DNA-binding domain, and how it is recruited to specific genomic sites is not fully understood. Here we carried out a mammalian two-hybrid screen and identified multiple transcriptional regulators potentially interacting with TET2.

Comprehensive chemical analysis of Schisandra chinensis by HPLC-DAD-MS combined with chemometrics.

The fruit of Schisandra chinensis, namely "Wuweizi" in China, is a well-known herbal medicine and health food. In this paper, an accurate and reliable high performance liquid chromatography coupled with diode array detection and mass spectrometry was developed for quality evaluation of Wuweizi. Nine lignans, including schisandrol A, schisandrol B, angeloylgomisin H, gomisin G, schisantherin A, schisanhenol, schisandrin A, schisandrin B, and schisandrin C were determined simultaneously in forty-three batches of Wuweizi samples collected from different localities.