Publications by authors named "A S Gorbatenko"
The mevalonate pathway produces essential lipid metabolites such as cholesterol. Although this pathway is negatively regulated by metabolic intermediates, little is known of the metabolites that positively regulate its activity. We found that the amino acid glutamine is required to activate the mevalonate pathway.
View Article and Find Full Text PDFInterleukin-1 receptor (IL-1R)-associated kinases (IRAKs) are core effectors of Toll-like receptors (TLRs) and IL-1R in innate immunity. Here, we found that IRAK4 and IRAK1 together inhibited DNA damage-induced cell death independently of TLR or IL-1R signaling. In human cancer cells, IRAK4 was activated downstream of ATR kinase in response to double-strand breaks (DSBs) induced by ionizing radiation (IR).
View Article and Find Full Text PDFArticle Synopsis
- IRAK proteins play a key role in the immune response but also activate in response to ionizing radiation (IR), leading to a protective anti-apoptotic effect in vertebrate cells.
- The activation of IRAK4 and IRAK1 occurs through a phosphorylation cascade independent of traditional immune receptors and results in IRAK1 being transported to the nucleus.
- This newly identified pathway involves detection of DNA damage and could be targeted to enhance the effectiveness of cancer treatments, particularly against tumor resistance to chemotherapy.
Article Synopsis
- Macrophages play an important role in inflammation, and their activity is influenced by histone modifications like H3K79 methylation, which DOT1L specifically regulates.
- In experiments using a DOT1L inhibitor and mice lacking Dot1l in myeloid cells, it was found that DOT1L is essential for controlling lipid biosynthesis genes, particularly SREBP1 and SREBP2.
- The absence of DOT1L leads to increased macrophage activation and reduced stability of atherosclerotic plaques, highlighting the significance of H3K79 methylation in inflammatory diseases.
Article Synopsis
- Increased metabolic acid production in many cancers disrupts pH balance, with V-ATPases playing a role in acid extrusion and cancer invasiveness.
- Research focused on the a3 subunit of V-ATPase in pancreatic ductal adenocarcinoma (PDAC) revealed higher levels in cancer cells compared to normal cells.
- Knockdown of a3 did not affect pH regulation or cell growth but surprisingly increased migration and invasion in PDAC cells, indicating it negatively regulates these processes possibly through its impact on extracellular matrix degradation.