CCG1/TAFII250 regulates epidermal growth factor receptor gene transcription in cell cycle mutant ts13
✍ Scribed by Gabriel A. Vargas; J. Mario Isas; Emanuelle Fantino; J. Jay Gargus; Harry T. Haigler
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 153 KB
- Volume
- 176
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
The epidermal growth factor receptor (EGFR) plays a critical role in normal growth and its overexpression is associated with several types of cancer. To learn more about regulation of the expression of this important receptor, we investigated the role of the TAF II 250 subunit of transcription factor IID in the transcription of the EGFR gene. The EGFR gene has a TATA-less promoter and TAF II 250 has previously been shown to have an important regulatory role in such promoters. The study was performed in the ts13 hamster cell line which has a temperature-sensitive mutation in the CCG1 gene that encodes TAF II 250. At the nonpermissive temperature, the transcription of a few cell cycle-dependent genes is depressed in ts13 cells while global RNA synthesis is unaffected. Using this model system, we found that EGFR promoter-driven luciferase expression in transiently transfected ts13 cells decreased 8, 25, and 50-fold after 12, 24, and 48 hours, respectively, at the nonpermissive temperature. The decrease was partially rescued by cotransfection with the wild-type CCG1 gene. The expression of endogenous EGFR also appeared to be regulated by TAF II 250-the maximum binding capacity of ts13 cells for 125 I-labeled EGF decreased approximately twofold when incubated for 2 days at the nonpermissive temperature. Placing these studies in the context of the current understanding of the TFIID transcription complex, we speculate that selective stimulation of EGFR gene transcription may be mediated by TAF II 250 interaction with enhancer-bound activators and the basal transcription machinery.