Schlafen family member 12 (SLFN12) (SLFN12)

Schlafen family member 12 (SLFN12) is a human protein belonging to the Schlafen family, which is characterized by a conserved Schlafen box domain and roles in regulating cell growth and immune functions [UniProt Q8IYM2]. SLFN12 has emerged as a significant therapeutic target in oncology through its interaction with Phosphodiesterase 3A (PDE3A) [PubMed: 28636597]. Certain small molecules, termed velcrins, act as molecular glues to stabilize the PDE3A-SLFN12 complex, which induces a conformational change in SLFN12 [Science: 369(6501)]. This activation triggers SLFN12's latent endoribonuclease activity, specifically targeting and cleaving tRNA-Leu-TAA [PubMed: 32439641]. The resulting depletion of functional tRNA leads to global protein synthesis inhibition and subsequent apoptosis in cancer cells [PubMed: 31606085]. Because this cytotoxic mechanism requires the co-expression of both PDE3A and SLFN12, these proteins serve as essential biomarkers for identifying sensitive tumor types, such as certain ovarian and lung cancers [PubMed: 28636597]. Therapeutic development is currently focused on optimizing velcrins to maximize cancer cell lethality while minimizing cardiovascular side effects associated with PDE3 inhibition [PubMed: 32439641].

Other names

SLFN12Schlafen 12

Molecular glue stabilization of the PDE3A-SLFN12 complex, which activates the latent endoribonuclease activity of SLFN12 to cleave tRNA-Leu-TAA, leading to translational arrest and apoptosis.