1415-GLI1 Palmitoylation in Sonic Hedgehog Medulloblastoma

This research identifies a novel biochemical mechanism where S-palmitoylation regulates the stability of the GLI1 protein, a key driver in Sonic Hedgehog medulloblastoma (MBSHH). The study demonstrates that the acyltransferase ZDHHC13 attaches a lipid group to GLI1, protecting it from degradation and fueling tumor progression. Conversely, the enzyme ABHD17A acts as a deacylase that removes this modification, destabilizing GLI1 and acting as a tumor suppressor. Using mouse models, the authors show that inhibiting ZDHHC13 extends survival and reduces tumor severity, while losing ABHD17A increases the incidence of cancer. These findings highlight the dynamic regulation of GLI1 as a potential therapeutic target for pediatric brain tumors. Ultimately, the paper establishes that the balance between palmitoylation and ubiquitination determines the signaling output of the SHH pathway.References:Shen T, Bao H, Wang J, et al. Dynamic S-palmitoylation of glioma-associated oncogene 1 regulates the incidence and progression of Sonic Hedgehog medulloblastoma[J]. Cell Death & Disease, 2026.前往小宇宙评论区与主播互动