Cell Cycle Control and Tumor Suppressors

我们已经克隆了ING家族基因(p33ING2、p47ING3、p29ING4和p29ING5)。ING家族基因有一个PhD-Finger基序，这是在核蛋白中发现的一个C4HC3类锌指基序，被认为参与染色质介导的转录调节。这个结构域的功能尚不清楚，但与LIM结构域类似，它可能参与蛋白质-蛋白质的相互作用，并对参与转录激活或抑制的多组分复合体的组装或活性是必需的。P33ING1蛋白是细胞周期、衰老和凋亡的调节因子。P33ING1的三个选择性剪接转录本编码p47ING1a、p33ING2/ING1L。与p33ING1b不同，p33ING2是由DNA损伤剂依托泊苷和新卡西诺抑素诱导的。P33ING1b和p22ING2通过诱导G1期细胞周期停滞和细胞凋亡，以p53依赖的方式负向调节细胞的生长和存活。P33ING2可显著增强P53的转录反式激活活性。此外，p33ING2的表达增加了P53在Lys-382的乙酰化。综上所述，p33ING2是一个DNA损伤诱导基因，它通过增强P53的乙酰化来激活P53，从而负向调节细胞的增殖。P47ING3、p29ING4和p29ING5各自通过染色质重塑调节P53转录功能。

We have cloned the ING family genes (p33ING2, p47ING3, p29ING4, and p29ING5). ING family genes have a PHD-finger motif, which is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in chromatin-mediated transcriptional regulation. The function of this domain is not yet known, but in analogy with the LIM domain, it could be involved in protein-protein interactions and necessary for the assembly or activity of multicomponent complexes involved in transcriptional activation or repression. The p33ING1 protein is a regulator of cell cycle, senescence, and apoptosis. Three alternatively spliced transcripts of p33ING1 encode p47ING1a, p33ING2/ING1L. Unlike p33ING1b, p33ING2 is induced by the DNA-damaging agents etoposide and neocarzinostatin. p33ING1b and p22ING2 negatively regulate cell growth and survival in a p53-dependent manner through the induction of G1-phase cell-cycle arrest and apoptosis. p33ING2 strongly enhances the transcriptional-transactivation activity of p53. Furthermore, p33ING2 expression increases the acetylation of p53 at Lys-382. Taken together, p33ING2 is a DNA damage-inducible gene that negatively regulates cell proliferation through the activation of p53 by enhancing its acetylation. p47ING3, p29ING4, and p29ING5 each regulate p53 transcriptional function by chromatin remodeling.