Schlafen family member 11 (SLFN11)

Schlafen family member 11 (SLFN11) is an interferon-inducible protein with a tripartite structure: an N-terminal endoribonuclease domain, a central linker domain, and a C-terminal helicase-like domain belonging to the superfamily I group[1][2][3][7]. SLFN11 acts as a critical restriction factor for a range of viruses by inhibiting viral protein translation in a tRNA/codon-usage-dependent manner[1][3]. It also binds to single-stranded DNA and tRNA, functioning as both a pattern recognition receptor in innate immunity and a modulator of nucleic acid metabolism. In cancer cells, high SLFN11 expression is a robust predictive biomarker for sensitivity to DNA-damaging chemotherapeutic agents, as SLFN11 blocks the recovery of stalled replication forks and disrupts the synthesis of DNA repair proteins by cleaving specific tRNAs, leading to apoptosis[1][2][3][4]. Its regulation is governed by phosphorylation-dependent conformational change and epigenetic silencing in some tumors[2][3]. SLFN11 is not a direct drug target but plays a decisive role in determining therapy response and represents a promising biomarker for personalized oncology.

Other names

Schlafen 11FLJ34922SLFN8/9 (deprecated)schlafen family member 11SLFN11

SLFN11 contributes to the mechanism of action of DNA-damaging chemotherapies and PARP inhibitors through: 1. Synthetic lethality: Tumor cells expressing SLFN11 are hypersensitive to agents that induce replication fork stalling, as SLFN11 irreversibly blocks stalled forks, preventing recovery and promoting cell death. 2. Translation inhibition: Endoribonucleolytic cleavage of tRNAs essential for DNA repair protein synthesis (ATM, ATR) leads to impaired response to DNA damage. 3. Immune activation: Direct binding and recognition of ssDNA motifs triggers immune responses and apoptosis.