Li Y, Lu J, Cohen D, Prochownik E V
Section of Hematology/Oncology, Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Oncogene. 2008 Mar 6;27(11):1599-609. doi: 10.1038/sj.onc.1210794. Epub 2007 Sep 17.
GpIbalpha, a subunit of the von Willebrand factor receptor, functions during blood clotting to promote platelet adhesion and activation. GpIbalpha is widely expressed, is positively regulated by c-Myc and is essential for the promotion of c-Myc-mediated chromosomal instability. We now show that GpIbalpha is also a classical oncoprotein in which its deregulated expression leads to transformation, reduced growth factor requirements, increased resistance to apoptosis, and, in primary cells, p53-dependent senescence. Finally, GpIbalpha also promotes double-stranded DNA breaks, and induces profound nuclear dysmorphology, indicating that, in addition to its direct transforming function, it displays genotoxicity at several distinct levels. These findings identify novel functions for GpIbalpha and pathways through which c-Myc mediates transformation and global genomic destabilization.
糖蛋白Ibα是血管性血友病因子受体的一个亚基，在血液凝固过程中发挥作用，促进血小板黏附和活化。糖蛋白Ibα广泛表达，受c-Myc正向调控，对促进c-Myc介导的染色体不稳定至关重要。我们现在表明，糖蛋白Ibα也是一种经典的癌蛋白，其表达失调会导致细胞转化、生长因子需求减少、抗凋亡能力增强，并且在原代细胞中会导致p53依赖性衰老。最后，糖蛋白Ibα还会促进双链DNA断裂，并诱导严重的核形态异常，这表明，除了其直接的转化功能外，它还在几个不同层面表现出基因毒性。这些发现确定了糖蛋白Ibα的新功能以及c-Myc介导细胞转化和全基因组不稳定的途径。
