A transcriptionally active pRb–E2F1–P/CAF signaling pathway is central to TGFβ-mediated apoptosis

• Published in: Cell death & disease 2012-10, Vol.3 (10), p.e407-e407
• Main Authors: Korah, J, Falah, N, Lacerte, A, Lebrun, J J
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Apoptosis - drug effects; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Line; E2F1 Transcription Factor - antagonists & inhibitors; E2F1 Transcription Factor - genetics; E2F1 Transcription Factor - metabolism; Hep G2 Cells; Humans; Immunology; Life Sciences; Mice; Mice, Knockout; Original; original-article; p300-CBP Transcription Factors - genetics; p300-CBP Transcription Factors - metabolism; Promoter Regions, Genetic - drug effects; Retinoblastoma Protein - genetics; Retinoblastoma Protein - metabolism; RNA Interference; RNA, Small Interfering - metabolism; Signal Transduction; Transcription, Genetic; Transforming Growth Factor beta - pharmacology
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2012.146

Transforming growth factor- β (TGF β ) modulates the expression of multiple apoptotic target genes; however, a common and central signaling pathway, acting downstream of TGF β and leading to cell death, has yet to be uncovered. Here, we show that TGF β -induced apoptosis in cancer cells requires the transcription factor E2F1 (E2 promoter-binding factor 1). Using the E2F1 knockout mouse model, we also found E2F1 to be required for TGF β -mediated apoptosis in normal cells. Moreover, we found TGF β to increase E2F1 protein stability, acting at the post-translational level. We further investigated the molecular mechanisms by which E2F1 contributes to TGF β -mediated apoptosis and found that TGF β treatment led to the formation of a transcriptionally active E2F1–pRb–P/CAF complex on multiple TGF β pro-apoptotic target gene promoters, thereby activating their transcription. Together, our findings define a novel process of gene activation by the TGF β -E2F1 signaling axis and highlight E2F1 as a central mediator of the TGF β apoptotic program.