Multiple PDE3A modulators act as molecular glues promoting PDE3A-SLFN12 interaction and induce SLFN12 dephosphorylation and cell death.

The canonical function of phosphodiesterase 3A (PDE3A) is to hydrolyze the phosphodiester bonds in second messenger molecules, such as cyclic AMP (cAMP) and cyclic guanosine monophosphate (cGMP). Recently, a phosphodiesterase-activity-independent role for PDE3A was reported. In this noncanonical function, PDE3A physically interacts with Schlafen 12 (SLFN12) upon treatment of cells with cytotoxic PDE3A modulators.

An alkaloid initiates phosphodiesterase 3A-schlafen 12 dependent apoptosis without affecting the phosphodiesterase activity.

The promotion of apoptosis in tumor cells is a popular strategy for developing anti-cancer drugs. Here, we demonstrate that the plant indole alkaloid natural product nauclefine induces apoptosis of diverse cancer cells via a PDE3A-SLFN12 dependent death pathway. Nauclefine binds PDE3A but does not inhibit the PDE3A's phosphodiesterase activity, thus representing a previously unknown type of PDE3A modulator that can initiate apoptosis without affecting PDE3A's canonical function.

Transcriptional responses and mechanisms of copper nanoparticle toxicology on zebrafish embryos.

Copper nanoparticles (CuNPs) are used widely due to their attractive antimicrobial properties. However, their biosafety and kinetics on vertebrate embryogenesis are still limited. In this study, CuNPs were revealed to induce eye hypoplasia and almost no digestive gut in zebrafish embryos in a dose-dependent manner.