E2F4 loss suppresses tumorigenesis in Rb mutant mice
Copyright policy )E2F4 loss suppresses tumorigenesis in Rb mutant mice
The E2F transcription factors mediate the activation or repression of key cell cycle regulatory genes under the control of the retinoblastoma protein (pRB) tumor suppressor and its relatives, p107 and p130. Here we investigate how E2F4, the major "repressive" E2F, contributes to pRB's tumor-suppressive properties. Remarkably, E2F4 loss suppresses the development of both pituitary and thyroid tumors in Rb(+/-) mice. Importantly, E2F4 loss also suppresses the inappropriate gene expression and proliferation of pRB-deficient cells. Biochemical analyses suggest that this tumor suppression occurs via a novel mechanism: E2F4 loss allows p107 and p130 to regulate the pRB-specific, activator E2Fs. We also detect these novel E2F complexes in pRB-deficient cells, suggesting that they play a significant role in the regulation of tumorigenesis in vivo.
- Massachusetts Institute of Technology United States
- Harvard University United States
- Harvard University, Department of Molecular and Cellular Biology United States
Cancer Research, Blotting, Western, Retinoblastoma-Like Protein p107, E2F4 Transcription Factor, Retinoblastoma Protein, Mice, Cyclin E, Animals, Pituitary Neoplasms, Cells, Cultured, Retinoblastoma-Like Protein p130, Reverse Transcriptase Polymerase Chain Reaction, Nuclear Proteins, Proteins, Cell Biology, Fibroblasts, Phosphoproteins, Mice, Mutant Strains, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, Oncology, Mutation
Cancer Research, Blotting, Western, Retinoblastoma-Like Protein p107, E2F4 Transcription Factor, Retinoblastoma Protein, Mice, Cyclin E, Animals, Pituitary Neoplasms, Cells, Cultured, Retinoblastoma-Like Protein p130, Reverse Transcriptase Polymerase Chain Reaction, Nuclear Proteins, Proteins, Cell Biology, Fibroblasts, Phosphoproteins, Mice, Mutant Strains, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, Oncology, Mutation
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