Zischka Hans, Kroemer Guido
Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
Technical University Munich, School of Medicine, Institute of Toxicology and Environmental Hygiene, Biedersteiner Strasse 29, 80802 Munich, Germany.
Cell Stress. 2020 Apr 24;4(5):92-94. doi: 10.15698/cst2020.05.218.
Toxic copper accumulation causes Wilson disease, but trace amounts of copper are required for cellular and organismal survival. In a recent paper Tsang (Nat Cell Biol, doi: 10.1038/s41556-020-0481-4) demonstrate that copper binds with high affinity to a designated interaction site in the pro-autophagic kinases ULK1 and ULK2. Chelation of copper or genetic deletion of this copper-binding site inhibits autophagy and hence reduces the fitness of KRAS-induced cancers. These findings suggest that copper chelation might constitute a novel therapeutic intervention on autophagy-dependent malignancies.
有毒的铜积累会导致威尔逊氏病,但细胞和机体的存活需要微量的铜。在最近的一篇论文中,曾(《自然细胞生物学》,doi: 10.1038/s41556-020-0481-4)证明铜以高亲和力与自噬前体激酶ULK1和ULK2中的一个指定相互作用位点结合。铜的螯合或该铜结合位点的基因缺失会抑制自噬,从而降低KRAS诱导的癌症的适应性。这些发现表明,铜螯合可能构成一种针对自噬依赖性恶性肿瘤的新型治疗干预措施。