Cell Cycle Control and Tumor Suppressors

我们已经克隆了ING家族基因（p33 ING 2、p47 ING 3、p29 ING 4和p29 ING 5）。ING家族基因具有PHD-指基序，这是在核蛋白中发现的C4 HC 3锌指样基序，被认为参与染色质介导的转录调节。该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-蛋白质相互作用，并且对于参与转录激活或抑制的多组分复合物的组装或活性是必需的。p33 ING 1蛋白是细胞周期、衰老和凋亡的调节因子。p33 ING 1的三个可变剪接转录本编码p47 ING 1a、p33 ING 2/ING 1 L。与p33 ING 1b不同，p33 ING 2是由DNA损伤剂依托泊苷和新制癌素诱导的。p33 ING 1b和p22 ING 2以p53依赖的方式通过诱导G1期细胞周期停滞和凋亡来负性调节细胞生长和存活。p33 ING 2强烈增强p53的转录-反式激活活性。此外，p33 ING 2表达增加了p53在Lys-382处的乙酰化。综上所述，p33 ING 2是一种DNA损伤诱导基因，通过增强其乙酰化激活p53来负调控细胞增殖。p47 ING 3、p29 ING 4和p29 ING 5分别通过染色质重塑调节p53的转录功能。

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.