- 作者: Zee-Fen Chang Duen-Yi Huang
- 作者服務機構: Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
- 中文摘要: --
- 英文摘要: As human diploid fibroblasts (HDFs) in culture senesce,the expression of thymidine kinase (TK) and the activityof its promoter become attenuated. Herein we analyzethe cis-elements involved in transcriptional activation ofthe hTK promoter, and show that the Sp1 binding sitelocated at-118/-113 and one CCAAT box located at ei-ther -71/-67 or -40/-36 are critical for maximal expres-sion of hTK promoter activity in young IMR-90 HDFs.However, the DNA binding activities to TK-CCAAT andSp1 were not defective in serum-stimulated senescentHDFs. On the other hand,treatment of young HDFs dur-ing the late G1 transition with a specific inhibitor ofCDK2, roscovitine, blocked the induction of TK RNAexpression. Because CDK2 remained inactive during se-rum stimulation in senescent HDFs, it is likely that theimpairment of TK expression in senescent HDFs duringserum stimulation is relevant to the inactivation of CDK2,rather than to the controlling mechanism at the level ofNF-Y and Sp1 activity.
- 中文關鍵字: --
- 英文關鍵字: Senescence. Thymidine kinase. Cell cycle