Abstract
We have previously shown that Sp1-mediated transcription is stimulated by Rb and repressed by cyclin D1. The stimulation of Sp1 transcriptional activity by Rb is conferred, in part, through a direct interaction with the TBP-associated factor TAF(II)250. Here we investigated the mechanism(s) through which cyclin D1 represses Sp1. We examined the ability of cyclin D1 to regulate transcription mediated by Gal4-Sp1 fusion proteins, which contain the Gal4 DNA-binding domain and Sp1 trans-activation domain(s). The domain of Sp1 sufficient to confer repression by cyclin D1 was mapped to a region important for interaction with TAF(II)110. We further demonstrate that TAF(II)250-cyclin D1 complexes can be immunoprecipitated from mammalian and baculovirus-infected insect cells and that recombinant GST-TAF(II)250 (amino acids 1-434) associates with cyclin D1 in vitro. Moreover, the overexpression of Rb or CDK4 reduced the level of TAF(II)250-cyclin D1 complex. The amino terminus of cyclin D1 (amino acids 1-100) was sufficient for association with TAF(II)250 and for repressing Sp1-mediated transcription. Taken together, the results suggest that cyclin D1 may regulate transcription by interacting directly or indirectly with TAF(II)250.
Original language | English (US) |
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Pages (from-to) | 239-247 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 18 |
Issue number | 1 |
DOIs | |
State | Published - Jan 7 1999 |
Externally published | Yes |
Keywords
- Cyclin D1
- Rb
- Sp1
- TAF(II)250