文章聚焦于铁死亡抑制蛋白FSP1(ferroptosis suppressor protein-1)的研究。研究人员通过筛选小分子库发现icFSP1这一新型 FSP1 抑制剂,它能诱导铁死亡,且作用机制不同于以往的iFSP1,不直接抑制FSP1酶活性,而是使FSP1发生亚细胞重定位并凝聚,进而促进FSP1相分离,引发脂质过氧化和铁死亡。这一过程依赖FSP
icFSPl-induced FSP1 condensates show droplet-like properties consistent with phase separation, an emerging and widespread mechanism to modulate biological activity7. N-terminal myristoylation, distinct amino acid residues and intrinsically disordered, low-complexity regions in FSP1 were identified to be ...
Phase separation of FSP1 promotes ferroptosis. Nature. 2023;619(7969):371–7. 151. Xie J, He H, Kong W, Li Z, Gao Z, Xie D, et al. Targeting androgen recep- tor phase separation to overcome antiandrogen resistance. Nat Chem Biol. 2022;18(12):1341–50. 152. Kamagata K, ...
48]. Phase separation of the type I subunit of protein kinase A (PKA RIα) mediates the homeostasis of intracellular 3’,5’-cyclic adenosine monophosphate (cAMP) and activation of the G protein coupled receptors; PKA RIα LLPS defect promotes cell growth and transformation...