K63-Linked Ubiquitination in Kinase Activation and Cancer

Ubiquitination has been demonstrated to play a pivotal role in multiple biological functions, which include cell growth, proliferation, apoptosis, DNA damage response, innate immune response, and neuronal degeneration. Although the role of ubiquitination in targeting proteins for proteasome-dependent degradation have been extensively studied and well-characterized, the critical non-proteolytic functions of ubiquitination, such as protein trafficking and kinase activation, involved in cell survival and cancer development, just start to emerge, In this review, we will summarize recent progresses in elucidating the non-proteolytic function of ubiquitination signaling in protein kinase activation and its implications in human cancers. The advancement in the understanding of the novel functions of ubiquitination in signal transduction pathways downstream of growth factor receptors may provide novel paradigms for the treatment of human cancers

Effects of curcumin on ion channels and transporters

Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione], a polyphenolic compound isolated from the rhizomes of Curcuma longa (turmeric), has been shown to exhibit a wide range of pharmacological activities including anti-inflammatory, anti-cancer, anti-oxidant, anti-atherosclerotic, anti-microbial, and wound healing effects. These activities of curcumin are based on its complex molecular structure and chemical features, as well as its ability to interact with multiple signaling molecules. The ability of curcumin to regulate ion channels and transporters was recognized a decade ago. The cystic fibrosis transmembrane conductance regulator (CFTR) is a well-studied ion channel target of curcumin. During the process of studying its anti-cancer properties, curcumin was found to inhibit ATP-binding cassette (ABC) family members including ABCA1, ABCB1, ABCC1, and ABCG2. Recent studies have revealed that many channels and transporters are modulated by curcumin, such as voltage-gated potassium (Kv) channels, high-voltage-gated Ca(2+) channels (HVGCC), volume-regulated anion channel (VRAC), Ca(2+) release-activated Ca(2+) channel (CRAC), aquaporin-4 (AQP-4), glucose transporters, etc., In this review, we aim to provide an overview of the interactions of curcumin with different types of ion channels and transporters and to help better understand and integrate the underlying molecular mechanisms of the multiple pharmacological activities of curcumin

Effectiveness of an anti-algal compound in eliminating an aquatic unicellular harmful algal Phaeocystis globosa

Phaeocystis globosa blooms can have negative effects on higher trophic levels in the marine ecosystem and consequently influence human activities. Strain KA22, identified as the bacterium Hahella, was isolated from coastal surface water and used to control P. globosa growth. A methanol extract from the bacteral cells showed strong algicidal activity. After purification, the compound showed a similar structure to prodigiosin when identified with Q-Exactive Orbitrap MS and nuclear magnetic resonance spectra. The compound showed algicidal activity against P. globosa with a 50% Lethal Dose (LD50) of 2.24 μg/mL. The prodigiosin was stable under heat and acid environment, and it could be degraded under alkaline environment and natural light condition. The growth rates of strain KA22 was fast in 2216E medium and the content of prodigiosin in this medium was more than 70 μg/mL after 16 h incubation. The compound showed particularly strong algicidal activity against Prorocentrum donghaiense, P. globosa and Heterosigma akashiwo, but having little effect on three other phytoplankton species tested. The results of our research could increase our knowledge on harmful algal bloom control compound and lead to further study on the mechanisms of the lysis effect on harmful algae