The mechanism of cell cycle regulation by thyroid hormone

聚ADP核糖聚合酶是细胞周期的重要调控因子之一。当这种酶被激活时，可以同时引入细胞周期中的转录和DNA合成的调节。前者通过激活作为转录因子靶点的基因的乙酰化来保持。本研究开展了甲状腺激素对该酶活性影响的研究，并寻找在转录过程中与该酶相互作用的因子。从细胞核提取物中可以分离出几种需要甲状腺激素受体作为配体依赖性转录因子的转录调控因子。然而，利用酵母双杂交系统，我们可以分离到一个严格控制细胞周期和转录的因子，它需要甲状腺激素受体。表征被广泛研究，我们确定的因素为极（ADP-核糖）聚合酶。该因子在细胞周期调控中起重要作用，其调控机制是诱导细胞凋亡。由该因子诱导的凋亡的引入被认为是细胞周期过度加速的阻遏物。抑制细胞周期的几种方法是已知的。在这种调控机制中，该因子作为一个因子输入细胞程序性死亡的信息。这一机制是非常重要的，因为细胞在DNA合成之前预先获得了过量的细胞周期，这些结果表明甲状腺激素可能在维持细胞周期单一化的持续引入中起重要作用。这些发现发表在1999年《生物化学杂志》和《摩尔细胞生物学》的两篇论文中。

Poly(ADP-ribose)polymerase is known as one of the important regulator of cell cycle. Regulation of transcription and DNA synthesis in cell cycle can be introduced simultaneously when this enzyme is activated. The former is held through the activation of acetylation of the gene which is target of the transcription factor. The researcher developed the study on the effect of thyroid hormone on the enzyme activity, and search the factors which interact with the enzyme during transcription. Several factors which control the transcription which require thyroid hormone receptor as a ligand-dependen transcription factor can be isolated from nuclear extract. However, by using yeast two-hybrid system, we can isolate a factor which strictly control the cell cycle and transcription which requires the thyroid hormone receptor. Characterizationis extensively studied, and we identified the factor as pole(ADP-ribose) polymerase. The factor plays an important role in the cell cycle regulation, and the mechanism of the regulation is induction of apoptosis. The introduction of apoptosis induced by this factor is held as a repressor for the excess acceleration of cell cycle. The several ways to repress the cell cycle are known. In the mechanism of this regulation, the factor functions as a factor inputs the information of programmed cell death. The mechanism is very important because the preaquisition of the excess cell cycle before DNA synthesis in the cell, and theses results indicate that thyroid hormone may play an important role in the maintaining the constant introduction of cell cycle singling. These findings are published in two papers in J. Biol. Chem. and Moll Cell Biol in 1999.