A Potent Transrepression Domain in the Retinoblastoma Protein Induces a Cell Cycle Arrest when Bound to E2F Sites

An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G1/S block. Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactiva...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-12, Vol.92 (25), p.11544-11548
Main Authors: Sellers, William R., Rodgers, Jennifer W., Kaelin, William G.
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Carrier Proteins
Cell Cycle
Cell Cycle Proteins
Cell growth
Cells, Cultured
Cellular biology
Chimeras
Deoxyribonucleic acid
DNA
DNA - metabolism
DNA-Binding Proteins
E2F Transcription Factors
E2F1 Transcription Factor
Genetic mutation
Humans
Kidney cells
Molecular Sequence Data
Mutation
Peptide Fragments - genetics
Peptide Fragments - metabolism
Plasmids
Promoter Regions, Genetic
Protein Binding
Protein Structure, Tertiary
Proteins
Recombinant Fusion Proteins
Repression
Repressor Proteins - genetics
Repressor Proteins - metabolism
Retinoblastoma Protein - genetics
Retinoblastoma Protein - metabolism
Retinoblastoma-Binding Protein 1
Transactivation
Transcription Factor DP1
Transcription Factors - genetics
Transcription Factors - metabolism
Transcriptional Activation
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Summary:An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G1/S block. Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactivation function, generate a complex capable of functioning as a transrepressor. Here we show that a chimera in which the E2F1 transactivation domain was replaced with the RB pocket could, in a DNA-binding and pocket-dependent manner, mimic the ability of RB to repress transcription and induce a cell cycle arrest. In contrast, a transdominant negative E2F1 mutant that is capable of blocking E2F-dependent transactivation did not. Fusion of the RB pocket to a heterologous DNA-binding domain unrelated to E2F likewise generated a transrepressor protein when scored against a suitable reporter. These results suggest that growth suppression by RB is due, at least in part, to transrepression mediated by the pocket domain bound to certain promoters via E2F.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.25.11544