Inhibitory mechanism of p53 transactivation by anaplastic lymphoma kinase(ALK) through direct p53 tyrosine phosphorylation

在淋巴瘤和肺癌中发现了某些染色体易位，它们的易位被认为促进了肿瘤的形成。我们发现易位基因既有激活致癌因子的能力，也有灭活抑癌基因的能力。此外，我们发现通过易位而被病理激活的基因通过其直接磷酸化来抑制一个重要的肿瘤抑制因子，而这些磷酸化通过增强肿瘤抑制因子的细胞质滞留来失活肿瘤抑制功能。

Certain chromosomal translocations have been found in lymphomas and lung cancers and their translocations are known to promote tumor formation. We found that translocated genes have both abilities to activate oncogenic factors and to inactivate tumor suppressors. Moreover, we found that pathologically activated genes by translocations inhibit an important tumor suppressor through its direct phosphorylations and that these phosphorylations inactivate the tumor-suppressive function through enhancement of cytoplasmic retention of the tumor suppressor.