ING1基因与肿瘤关系的研究进展

Research progress of ING1 gene and tumor

肿瘤的发生是一个多基因参与的多步骤的复杂过程,肿瘤抑制基因可能是抑制肿瘤发生的重要保护机制。ING1是1996年发现的一个候选抑癌基因,定位于人染色体13q33～34。ING1mRNA有ING1a、ING1b和ING1c三种变位剪接形式,分别编码三种不同的蛋白质:p47ING1a、p33ING1b和p24ING1c,其中p33ING1b是目前肿瘤研究的热点。ING1蛋白在正常细胞主要位于细胞核内,部分肿瘤细胞则在细胞质表达较多。ING1具有调控细胞周期、诱导细胞凋亡和DNA损伤修复的作用。其中,p33ING1通过调控细胞周期负向调节细胞生长而p47ING1a过表达则对细胞生长无明显影响。p33ING1b过量表达可以促进p21WAF1表达,协同p53引起细胞周期阻滞从而抑制肿瘤细胞生长。ING1基因可能是通过乙酰化依赖通路的活性调节来改变基因的表达,参与多种过程的调控。ING1编码的蛋白通过组蛋白乙酰转移酶(HATs)和组蛋白去乙酰化酶(HDACs)参与染色质的重塑,在DNA损伤修复方面发挥重要作用。ING1基因与脑瘤、肝癌和胃癌等多种肿瘤的发生发展有关。ING1基因的结构特点、生物学功能与肿瘤的发生发展密切相关。

The occurrence of tumor is process involving many genes and courses a complicated Among these genes, the tumor suppressor genes play a great role to inhibit the development of tumor. ING1 was a candidate tumor suppressor gene which was found in 1996. It locates in 13q33-34 on human chromosomal and encodes three different proteins. They are p47^ING1a , p33^ING1b and p24^ING1c. Among them, p33^ING1b is currently hotspot of the tumor research. The ING1 protein exists in nucleoli of the normal cells and cytoplasm of some tumor cells. ING1 can regulate cell cycle, induce cell apoptosis and repair DNA damage, p33^ING1 is involved in the regulation of cell cycle and negate the cell growth. However the over expression of p47^ING1adoes not distinctively effect the cell growth. The over expression of p33^ING1b can promote the expression of p21^WAP1 which cooperates with p53 to restrain the cell growth by regulating the activity of the acetylating depended pathway. The ING1 protein involves in rebuilding of chromatin to prepare DNA damage with HATs and HDACs. The abnormal expression of ING1 is closely correlative with the onset of encephaloma, liver cancer, gastric cancer and etc. This review focuses on the structure and characters of ING1 and its biological functions as well as the the relationship between ING1 and the onset and development of tumor.