Rushton J J, Steinman R A, Robbins P D
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pennsylvania 15261, USA.
Cell Growth Differ. 1997 Oct;8(10):1099-104.
The TATA-binding protein-associated factor TAF(II)250, the largest subunit of TFIID, was first identified as the cell cycle regulatory protein CCG1. The ts13 Syrian hamster ovary fibroblast cell line, which contains a temperature-sensitive point mutation in TAF(II)250/CCG1, is arrested in G1 following a shift to the nonpermissive temperature. Here we demonstrate that the level of the D-type cyclins, in particular D1, was reduced, whereas the level of the cyclin-dependent kinase inhibitor p21 was stimulated in ts13 cells at the nonpermissive temperature. The levels of expression of cyclins A and E were not affected by temperature shift. We further show that at least part of the regulation of D1 and p21 levels in ts13 cells is mediated at the level of transcription initiation. These results suggest that the effect of the temperature-sensitive mutation TAF(II)250 on cell growth can be mediated through the differential regulation of transcription of specific cell growth regulatory genes, such as cyclin D1 and p21.
TATA 结合蛋白相关因子 TAF(II)250 是 TFIID 的最大亚基，最初被鉴定为细胞周期调节蛋白 CCG1。ts13 叙利亚仓鼠卵巢成纤维细胞系在 TAF(II)250/CCG1 中含有一个温度敏感型点突变，在转移到非允许温度后会停滞在 G1 期。在此我们证明，在非允许温度下，ts13 细胞中 D 型细胞周期蛋白，特别是 D1 的水平降低，而细胞周期蛋白依赖性激酶抑制剂 p21 的水平升高。细胞周期蛋白 A 和 E 的表达水平不受温度变化的影响。我们进一步表明，ts13 细胞中 D1 和 p21 水平的至少部分调节是在转录起始水平介导的。这些结果表明，温度敏感型突变 TAF(II)250 对细胞生长的影响可通过特定细胞生长调节基因（如细胞周期蛋白 D1 和 p21）转录的差异调节来介导。
