Signaling functions of Fanconi anemia proteins

Fanconi anemia (FA) is characterized by bone marrow failure, yet its molecular basis remains unclear. This work identifies two non–DNA‑repair functions of FA proteins critical for hematopoietic cell survival. First, FANCC regulates Toll‑like receptor 8, and its loss drives excess TNF‑α production in FA cells. Second, FANCC, FANCG, and FANCD2 are required for proper STAT5 activation, involving inducible interactions that enable nuclear translocation of phosphorylated STAT5. Because STAT5 signaling is essential for hematopoietic stem cell survival, these defects likely contribute to marrow failure. These findings demonstrate multifunctional roles for FA proteins beyond the canonical nuclear core‑complex pathway.