Transforming growth factor-β regulation of retinoblastoma gene product and E2F transcription factor during cell cycle progression in mouse fibroblasts
✍ Scribed by Dr. Tae-Aug Kim; Michael J. Ravitz; Charles E. Wenner
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 1013 KB
- Volume
- 160
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
The mechanism by which transforming growth factor beta (TGFP) exerts growth stirnulatory effects was examined in C3HIlOT112 mouse fibroblasts by study of cell cycle regulation of the retinoblastoma gene product (pl 1 ORb) and transcriptional regulation of the p l 1 OKb-associated transcription factor, E2F. Northern blotting analysis shows that TGFP and/or epidermal growth factor (EGF) stimulate by three to sixfold the level of Rb mRNA which is also reflected by the increased levels of p l loRb. p l loRh becomes phosphorylated in mid-C1 and further phosphorylated at the G,/S transition. Hyperphosphorylation of p l loRb by TGFP can be observed when cells are in S phase. TGFP stimulates by three to fourfold the activity of cdk2 kinase consistent with the observed phosphorylation of p l 1 ORb and also with the possibility that the kinase is involved in phosphorylating p l toKb close to the G,/S transition. Thus, TGFP as a growth stimulator induces, as does ECF, the phosphorylation of p l 1 OKb during cell cycle progression. Transient transfection of E2F promoter constructs was used to analyze the effect of TGFP on the modulation of E2F-mediated transcription. The data revealed that TGFP can stimulate wild-type adenoviral E2 promoter activity by 12-fold. Taken together, TGFP-induced phosphorylation of p l loRb in mouse fibroblasts appears to exert a positive regulatory function upon genes that have a pivotal role in the G,/S transition of the cell cycle.