Chen Yen-Chung, Teng Shu-Chun, Wu Kou-Juey
Institutes of Biochemistry & Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Cancer Invest. 2009 Jan;27(1):24-8. doi: 10.1080/07357900802027081.
Telomeric repeat binding factor 1 (TRF1) belongs to the shelterin complex, which modulates the telomere structures. Akt/protein kinase B activation caused genomic instability and contributes to tumorigenesis, although the molecular mechanism remained little known. Here, we show the direct interaction between Akt and TRF1. In vitro kinase assays showed the phosphorylation of a putative Akt phosphorylation site (Threonine 273) in wild type TRF1, but not the mutant TRF1 (T273A), by Akt. Overexpression of Akt decreased telomere length in a HTC cell line. These results indicate that Akt plays an important role in telomere length regulation, contributing to genomic instability and tumorigenesis.
端粒重复序列结合因子1（TRF1）属于保护帽复合体，该复合体可调节端粒结构。尽管分子机制仍鲜为人知，但Akt/蛋白激酶B的激活会导致基因组不稳定并促进肿瘤发生。在此，我们展示了Akt与TRF1之间的直接相互作用。体外激酶分析表明，Akt可使野生型TRF1中一个假定的Akt磷酸化位点（苏氨酸273）发生磷酸化，但不能使突变型TRF1（T273A）发生磷酸化。Akt的过表达会使HTC细胞系中的端粒长度缩短。这些结果表明，Akt在端粒长度调节中起重要作用，导致基因组不稳定并促进肿瘤发生。
