ACS DIVISION OF BIOLOGICAL CHEMISTRY

August 6th, 2020 by

August 5th, 2020 by Chen Mozes† and Michael M. Meijler*†

August 2nd, 2020 by Ronald R. Breaker*

July 28th, 2020 by Vivian W Tang, Ambika V. Nadkarni, William M Brieher

Cofilin is an actin filament severing protein necessary for fast actin turnover dynamics. Coronin and Aip1 promote cofilin mediated actin filament disassembly, but the mechanism is somewhat controversial. An early model proposed that the combination of cofilin, coronin, and Aip1 disassembled filaments in bursts. A subsequent study only reported severing. Here, we used electron microscopy to show that actin filaments convert directly into globular material. A monomer trap assay also shows that the combination of all three factors produces actin monomers faster than any two factors alone. We show that coronin accelerates the release of inorganic phosphate from actin filaments and promotes highly cooperative cofilin binding to actin to create long stretches of polymer with a hypertwisted morphology. Aip1 attacks these hypertwisted regions along their sides, disintegrating them into monomers or short oligomers. The results are consistent with a catastrophic mode of disassembly, not enhanced severing alone.

July 27th, 2020 by Lina Wang

Nature Chemical Biology, Published online: 27 July 2020; doi:10.1038/s41589-020-0601-2

NADP can directly bind with FTO and enhance its m6A demethylase activity, thus affecting RNA m6A modification and adipogenesis.

July 27th, 2020 by Aravind Natarajan

Nature Chemical Biology, Published online: 27 July 2020; doi:10.1038/s41589-020-0595-9

An orthogonal O-glycan biosynthesis system was engineered in Escherichia coli to support the production of glycoproteins displaying human mucin O-glycans, including Tn antigens, in living bacteria and in cell-free extracts.

July 27th, 2020 by Jakob Gebel

Nature Chemical Biology, Published online: 27 July 2020; doi:10.1038/s41589-020-0600-3

TAp63α monitors the genome integrity in oocytes. After DNA damage, TAp63α is activated, involving multiple phosphorylation steps by CK1 with different kinetics due to an unusual CK1/TAp63α interaction in which the product of one step inhibits the next.

July 27th, 2020 by Godwin A. Aleku

Nature Chemical Biology, Published online: 27 July 2020; doi:10.1038/s41589-020-0603-0

Biocatalytic cascade reactions using engineered variants of ferulic acid decarboxylase coupled to carboxylic acid reductase utilize carbon dioxide fixation to enable the carboxylation and functionalization of styrene and other aromatic compounds.

July 24th, 2020 by Kangdi Li, Ting Liu, Jie Chen, Huying Ni, Wenhua Li

Cancer-associated fibroblasts (CAFs) play a critical role in the coevolution of breast tumor cells and their microenvironment by modifying cellular compartments and regulating cancer cell functions via stromal-epithelial dialogue. However, the relationship and interaction between stromal and epithelial cells are still poorly understood. Herein, we revealed that breast cancer cells have a stronger ability to activate fibroblasts and transform them into myofibroblasts (CAF-like) than normal breast epithelial cells, and this stronger ability occurs through paracrine signaling. In turn, myofibroblasts promote the proliferation, epithelial-to-mesenchymal transition (EMT), and stemness of breast cancer cells. Detailed regulatory mechanisms showed that, compared to normal cells, Survivin is overexpressed in breast cancer cells and secreted extracellularly in the form of exosomes, which are then internalized by fibroblasts. Breast cancer cell-derived Survivin upregulates SOD1 expression in fibroblasts and then converts them into myofibroblasts, conversely inducing breast cancer progression in vitro and in vivo. Thus, our results indicate that Survivin acts as an activator of the tumor microenvironment and that SOD1 upregulation in fibroblasts can promote breast cancer progression. These results suggest that targeting Survivin and SOD1 may be a potential therapeutic strategy for breast cancer.

July 24th, 2020 by Trieu Le, Son C Le, Yang Zhang, Pengfei Liang, Huanghe Yang

TMEM16 Ca2+-activated phospholipid scramblases (CaPLSases) mediate rapid trans-membrane phospholipid flip-flop and as such play essential roles in various physiological and pathological processes such as blood coagulation, skeletal development, viral infection, cell-cell fusion and ataxia. Pharmacological tools specifically targeting TMEM16 CaPLSases are urgently needed to understand these novel membrane transporters and their contributions to health and disease. Tannic acid (TA) and epigallocatechin gallate (EGCG) were recently reported as promising TMEM16F CaPLSase inhibitors. However, our present study shows that TA and EGCG do not inhibit the phospholipid scrambling or ion conduction activities of the dual-functional TMEM16F. Instead, we found that TA and EGCG mainly acted as fluorescence quenchers that rapidly suppress the fluorophores conjugated to Annexin V (AnV), a phosphatidylserine (PS) binding probe commonly used to report on TMEM16 CaPLSase activity. These data demonstrate the false positive effects of TA and EGCG on inhibiting TMEM16F phospholipid scrambling and discourage the use of these polyphenols as CaPLSase inhibitors. Appropriate controls as well as a combination of both fluorescence imaging and electrophysiological validation are necessary in future endeavors to develop TMEM16 CaPLSase inhibitors.