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，它们的易位促进了肿瘤的形成。我们发现易位基因同时具有激活致癌因子和灭活肿瘤抑制因子的能力。此外，我们发现易位的病理激活基因通过其直接磷酸化抑制重要的肿瘤抑制因子，并且这些磷酸化通过增强肿瘤抑制因子的细胞质保留而使肿瘤抑制功能失活。

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.