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The Hippo pathway is a key regulator of tissue homeostasis, organ size and cancer. Identification of microcolin B and its analog molecules as Hippo pathway activators connects PtdIns4P-dependent lipid signaling with the Hippo pathway, suggesting potential targets for cancer therapy.

The marine compound microcolin B stimulates the Hippo pathway and selectively kills YAP-dependent cancer cells by inhibiting phosphatidylinositol transfer protein and depleting plasma membrane phosphatidylinositol-4-phosphate.

Aldehyde dehydrogenase 1B1-specific small-molecule inhibitors are identified that block the growth of colon cancer spheroids and organoids and are shown to potentially regulate mitochondrial metabolism and ribosomal function.

This Perspective discussed selective partitioning behaviors of biomolecules and small molecules and proposed that understanding the chemical properties that control their interactions within the condensates would promote drug development.

Several venomous predators and pathogens use insulins to capture prey and to manipulate host physiology. This Review provides an overview of the discovery and potential biomedical application of these and other weaponized hormones found in nature.

Sea stars and sea cucumbers biosynthesize protective glycosylated steroids and triterpenes via divergent oxidosqualene cyclases (OSCs) that produce these distinct saponins in different species as well as in different tissues of a single species.

Using combined methods of modern chemical protein synthesis and structural biology, Ai et al. found a crosstalk mechanism of histone modifications, by which H2BK34ub stimulates the activity of the H3K79 methyltransferase Dot1L through inducing nucleosome distortion.

Antigen loading onto class I major histocompatibility complex (MHC-I) proteins relies on chaperones and protein flexibility. Researchers now provide new insight into the process, especially for the intriguing ‘non-classical’ MHC-I protein MR1, with implications for fundamental immunology and the development of novel immunotherapies.

Biochemical and structural approaches define how the chaperone TAPBPR interacts with MR1 molecules, including empty and ligand-loaded MR1, and facilitates presentation of metabolite-derived antigen ligands by MR1 complexes.

Carbon dioxide (CO₂) is a product of cellular respiration that can also serve as a post-translational modification (PTM) through covalent protein modification. A new chemoproteomic strategy enables the capture of functional CO₂-dependent carboxylation on lysine residues of proteins.

Comprehensive structural biology analysis of seven members of the S1 carbohydrate sulfatase family derived from human gut microbiome Bacteroides reveals mechanisms of glycan recognition and sulfate hydrolysis.

B-cell activation reprograms the TCA cycle and reduces cellular fumarate levels. Increased fumarate caused by fumarase inhibition or dimethyl-fumarate treatment directly succinates and inhibits LYN, leading to impaired B-cell activation and function.

Using isocyanic acid as a CO₂ analog generates a stable mimic of lysine carboxylation, enabling development of a quantitative chemoproteomic approach to identify this modification in proteins and explore the lysine carboxylome of a cyanobacterium.

MNK2 was identified as the target of a small molecule named CID661578 that can stimulate pancreatic β-cell generation in zebrafish, pig and human organoids. CID661578 prevents MNK2 from binding to eIF4G in the translation initiation complex.

The zinc-sensor protein Zur in a marine cyanobacterium is distinct from those in other bacteria in structure and location of its sensory zinc site, and facilitates growth across a range of zinc concentrations via activation of a metallothionein gene.

Using nanobodies labeled with FRET fluorophores, the authors show the presence and activation of GPCR mGlu2 and mGlu4 dimers in mouse brain samples and reveal that mGlu2–mGlu4 is the major form of mGlu4-containing dimers outside the cerebellum.