Protein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Published: March 2024
AI Article Synopsis
Article Abstract
Proteasome subunit hRpn13 is partially proteolyzed in certain cancer cell types to generate hRpn13 by degradation of its UCHL5/Uch37-binding DEUBAD domain and retention of an intact proteasome- and ubiquitin-binding Pru domain. By using structure-guided virtual screening, we identify an hRpn13 binder (XL44) and solve its structure ligated to hRpn13 Pru by integrated X-ray crystallography and NMR to reveal its targeting mechanism. Surprisingly, hRpn13 is depleted in myeloma cells following treatment with XL44. TMT-MS experiments reveal a select group of off-targets, including PCNA clamp-associated factor PCLAF and ribonucleoside-diphosphate reductase subunit M2 (RRM2), that are similarly depleted by XL44 treatment. XL44 induces hRpn13-dependent apoptosis and also restricts cell viability by a PCLAF-dependent mechanism. A KEN box, but not ubiquitination, is required for XL44-induced depletion of PCLAF. Here, we show that XL44 induces ubiquitin-dependent loss of hRpn13 and ubiquitin-independent loss of select KEN box containing proteins.
Red tide is caused by the accumulation of Karenia (K.) brevis, which produces brevetoxin (BTx), a neurotoxin. Excreted BTx is incorporated into sea spray aerosol (SSA), which is created from the bursting of bubbles at the ocean's surface.
Background: Surveillance of the host-anopheline mosquitoes' interaction is important for assessing malaria transmission risk and guiding vector control. We assume that changes in malaria vector species' feeding habits, as well as the surrounding environment, have a substantial impact on varied malaria transmission. In this study, we determined the vertebrate host feeding patterns of anopheline mosquitoes to characterize entomologic risk factors for malaria in Jabi Tehnan, Northwestern Ethiopia.
- Improved tools like DNA barcoding reveal that mosquitoes, specifically malaria vectors in Kenya, feed on plants much more than previously thought, with a 41% feeding rate versus a low 2.8% through traditional methods.
- The study found that the presence of the malaria parasite Plasmodium falciparum affects the sugar levels in mosquitoes, and that these insects primarily feed on acacia plants, particularly Vachellia tortilis.
- The findings point to the important role of nutrient content and scent from plants in attracting mosquitoes, and these insights could help develop effective strategies for controlling malaria through odor-based traps and bait.
Bee products, abundant in bioactive ingredients, have been utilized in both traditional and contemporary medicine. Their antioxidant, antimicrobial, and anti-inflammatory properties make them valuable for food, preservation, and cosmetics applications. Honeybees are a vast reservoir of potentially beneficial products such as honey, bee pollen, bee bread, beeswax, bee venom, and royal jelly.
Inflammation-induced choroidal neovascularization followed by the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPEs) is a cause of neovascular age-related macular degeneration (nAMD). RPE-derived myofibroblasts overproduce extracellular matrix, leading to subretinal fibrosis. We already have demonstrated that benzylphenylurea (BPU) derivatives inhibit the function of cancer-associated fibroblasts.
