Journal
EMBO JOURNAL
Volume 21, Issue 18, Pages 4927-4937Publisher
WILEY
DOI: 10.1093/emboj/cdf501
Keywords
cell cycle; Drosophila; E2F; RBF; Retinoblastoma
Categories
Funding
- NCI NIH HHS [F32 CA88474, F32 CA93045] Funding Source: Medline
- NIGMS NIH HHS [R01 GM053203, GM53203] Funding Source: Medline
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RBF1, a Drosophila pRB family homolog, is required for cell cycle arrest and the regulation of E2F-dependent transcription. Here, we describe the properties of RBF2, a second family member. RBF2 represses E2F transcription and is present at E2F-regulated promoters. Analysis of in vivo protein complexes reveals that RBF1 and RBF2 interact with different subsets of E2F proteins. dE2F1, a potent transcriptional activator, is regulated specifically by RBF1. In contrast, RBF2 binds exclusively to dE2F2, a form of E2F that functions as a transcriptional repressor. We find that RBF2-mediated repression requires dE2F2. More over, RBF2 and dE2F2 act synergistically to antagonize dE2F1-mediated activation, and they co-operate to block S phase progression in transgenic animals. The network of interactions between RBF1 or RBF2 and dE2F1 or dE2F2 reveals how the activities of these proteins are integrated. These results suggest that there is a remarkable degree of symmetry in the arrangement of E2F and RB family members in mammalian cells and in Drosophila.
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