Reviews & Analysis

Biologic drugs that modulate the immune system have revolutionized the therapeutic landscape for several selected cancer types. A new study reports an image-based assay system to monitor cell–cell interactions, identifying small-molecule compounds with immunomodulatory capacity.

Proteolysis-targeting chimera (PROTACs) are synthetic molecules that recruit neo-substrate proteins to a ubiquitin ligase for ubiquitination and subsequent degradation. Structural insight into the VHL–MZ1–BRD4 complex reveals how the rationally designed MZ1–PROTAC molecule mediates degradation of an unnatural protein substrate.

A new signal–receptor pair involved in regulating biofilm formation and virulence was detected in Vibrio cholerae. Both the signal and the transcription factor belong to common classes of natural products and receptor proteins, suggesting widespread importance of related systems in nature.

In early-stage developing neurons, the cAMP–PKA (protein kinase A) signaling pathway is strongly inhibited. This negative control is later removed, unleashing cAMP–PKA signaling, particularly in distal axonal parts, thus allowing for axonal growth.

Pharmacological chaperones are small drugs that stabilize a protein's fold and are being developed to treat diseases arising from protein misfolding. A mathematical framework to model their activity in cells enables insight into their mechanism and capacity to rescue protein foldedness.

Systematically modifying biological assembly lines for the synthesis of novel products remains a challenge. Structural insights and computational modeling have now paved the way for efficient redesigns of giant fatty acid synthases.

A new mechanism of functional crosstalk between two distinct G-protein-coupled receptors (GPCRs)—the parathyroid hormone receptor (PTHR) and β₂-adrenergic receptor (β₂ Ar)—that occurs at the level of G protein βγ subunits and a specific adenylyl cyclase isoform is identified. This crosstalk augments cAMP signaling by the PTHR from endosomes, and thus promotes the actions of PTH ligands in bone target cells.

Bioengineers have endowed a consortium of human cells with an artificial sense of smell, enabling the cells to detect, quantify, and remember the presence of gaseous volatile compounds in their environment.

New small-molecule inhibitors of the histone methyltransferase PRC2 interfere with the allosteric activation of enzymatic activity. These compounds are effective against PRC2-dependent tumors that are resistant to catalytic inhibitors and provide important new tools for altering chromatin regulation.

Differential redox regulation of kinase isoforms serves to provide intricate control of cellular signaling events. In a new study, a single isoform of Akt, Akt3, is shown to be preferentially modified by lipid-derived electrophiles to modulate downstream signaling events in mammalian cells and zebrafish.

The ability to measure the binding of a compound to its intended target in live cells or tissue is a critical parameter for drug discovery. A new method using polarized light microscopy adds to the current toolbox by enabling monitoring of target engagement in vitro and in vivo at single-cell resolution.

Sensing and responding to diverse extracellular signals is a crucial aspect of cellular decision-making that is currently lacking in the synthetic biology toolkit. The development of modular receptor platforms allows for the rewiring of cellular input–output relationships.

Nitrogenase has the canonical ability to reduce N₂ to NH₃, but under certain conditions, either in vitro or in vivo, it has the additional capability to convert CO₂ to CO and CO to light hydrocarbons.

A phosphodiesterase, CdnP, from Mycobacterium tuberculosis (M. tb.) helps the pathogen evade immune detection by degrading the second messenger cyclic di-AMP that alerts the host to its presence. Genetic knockout of CdnP dampens the virulence of the pathogen, suggesting that CdnP inhibitors are potential anti–M. tb. therapeutics.