肿瘤转移抑制基因Tip30/CC3研究进展

Progress on Tumor Metastasis Suppressor Gene Tip30/CC3

Tip30/CC3是新发现的一种与肿瘤转移抑制相关的基因,在人类的多种组织如心、脑、肺、肾、骨骼肌和胰腺中均有表达,但在多种肿瘤组织中表达下降或缺失。研究表明,一方面,Tip30/CC3是一种转录辅助因子,具有丝/苏氨酸激酶活性,可以和RNA聚合酶Ⅱ最大亚基结合并磷酸化其C末端的七肽重复基序,在特定生理病理环境下调节细胞凋亡和血管生成相关基因的表达,从而促进细胞凋亡和抑制肿瘤转移;另一方面,Tip30/CC3能够以RanGTP非依赖形式直接与Importinβ家族成员及核孔蛋白相结合,抑制核转运蛋白的功能,通过抑制核物质输入促进细胞凋亡来发挥抑癌作用。文章就Tip30/CC3基因的发现、结构特点、与肿瘤的关系、功能、作用机理和应用前景进行了综述。

Tip30/CC3 is a novel gene associated with the suppression of tumor metastasis. Its expression has been detected in many human normal tissues such as heart, brain, lung, kidney, skeletal muscle and pancreas. However, in some tumor types, its expression was found to be decreased. Studies revealed that, on one hand, TIP30/CC3 was a transcriptional cofactor with Ser/Thr protein kinase activity, that could bind to the largest RNA polymerase Ⅱ subunit and phosphorylate the heptapeptide repeats of the C-terminal domain of its, regulating expression of genes involved in apoptosis and angiogenesis to promote apoptosis and suppress tumor growth and metastasis on the specially physiological and pathological manners on the other hand, TIP30/CC3 may bind directly to the members of Importinβ family in a RanGTP-insensitive manner and associate with nucleoporins to suppress tumor growth through promoting apoptosis induced by the inhibition of nuclear transport. This review summarized the discovery of the Tip30/CC3 gene, the property of structure, the relation with tumor, function,mechanism of action and prospect.