Kourtis Nikos, Strikoudis Alexandros, Aifantis Iannis
Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Curr Opin Cell Biol. 2015 Dec;37:28-34. doi: 10.1016/j.ceb.2015.09.003. Epub 2015 Sep 28.
Protein degradation plays key roles in diverse pathways in cell division, growth and differentiation. Aberrant stabilization of crucial proteins participating in oncogenic pathways is often observed in cancer. The importance of proper protein turnover is exemplified by the SCF(Fbxw7) ubiquitin ligase, which is frequently mutated in human cancer, including T cell acute lymphoblastic leukemia. Recent studies have revealed novel substrates of Fbxw7 and shed light on its role on differentiation of stem cells and expansion of stem-cell-like cells driving tumorigenesis. Detailed understanding of the contribution of the Fbxw7-regulated network of proteins in initiation and progression of cancer will facilitate the identification of candidate intervention targets in human cancer.
蛋白质降解在细胞分裂、生长和分化的多种途径中发挥着关键作用。在癌症中经常观察到参与致癌途径的关键蛋白质的异常稳定。参与致癌途径的关键蛋白质的异常稳定在癌症中经常被观察到。SCF（Fbxw7）泛素连接酶体现了适当蛋白质周转的重要性，该酶在包括T细胞急性淋巴细胞白血病在内的人类癌症中经常发生突变。最近的研究揭示了Fbxw7的新底物，并阐明了其在干细胞分化和驱动肿瘤发生的干细胞样细胞扩增中的作用。深入了解Fbxw7调节的蛋白质网络在癌症发生和发展中的作用，将有助于确定人类癌症中的候选干预靶点。
