Modulation of Akt kinase activity by ubiquitination

丝氨酸苏氨酸Akt是核心的细胞内存活调节因子。本研究证明了NS 1与Akt的功能相互作用，阐明了NS 1与Akt在流感病毒生物化学分析中的功能重要性。本研究通过生物化学分析、生物信息学分析和转基因血管肉瘤小鼠的制备，阐明了TCL 1b在体内外均具有Akt激酶共激活剂和致瘤性的功能。通过免疫组化，大多数人血管肉瘤样本和各种癌组织均被抗TCL 1b和抗磷酸化Akt抗体阳性染色。此外，基于TCL 1b结构的抑制剂“TCL 1b-Akt-in”抑制Akt激酶活性，因此抑制肉瘤的细胞增殖。本研究发现TCL 1b具有致瘤性，因此可作为治疗人类肿瘤性疾病的新靶点。

Serine threonine Akt is a core intra-cellular survival regulator. In this study, we demonstrated that the functional interaction of NS1 with Akt and clarified that the functional importance of influenza virus NS1 with Akt in biocmical analysis. The results together supported the functional importance of influenza virus NS1 with Akt.We clarified that TCL1b functions as an Akt kinase co-activator and exhibitsoncogenicity both in vitro and in vivo using biochemical analysis, bioinformatics, and generation of TCL1b transgenic mice which resulted in angiosarcoma. By immunohistochemistry, most of human angiosarcoma samples and various cancer tissues were positively stained by both anti-TCL1b and anti-phospho-Akt antibodies. Moreover,TCL1b structure-based inhibitor “TCL1b-Akt-in” inhibited Akt kinase activity, hence, suppressed cellular proliferation of sarcoma. The current study disclosed TCL1b bears oncogenicity, and hence serves as a novel therapeutic target for human neoplasticdiseases.