The E2F family of transcriptional regulators consists of six different members. Analysis of E2F-regulated promoters by using cultured cells suggests that E2Fs may have redundant functions. However, animal studies have shown that loss of individual E2Fs can have distinct biological consequences. Such seemingly conflicting results could be due to a difference in E2F-mediated regulation in cell cu...

The Hippo/Yki and RB/E2F pathways both regulate tissue growth by affecting cell proliferation and survival, but interactions between these parallel control systems are poorly defined. In this study, we demonstrate that interaction between Drosophila E2F1 and Sd disrupts Yki/Sd complex formation and thereby suppresses Yki target gene expression. RBF modifies these effects by reducing E2F1/Sd int...

During lytic infections HHV-6A and HHV-6B disrupt E2F1-Rb complexes by Rb degradation, releasing E2F1 and driving the infected cells toward the S-phase. Whereas upon infection E2F1 and its cofactor DP1 were up-regulated, additional E2F responsive genes were expressed differentially in various cells. E2F binding sites were identified in promoters of several HHV-6 genes, including the U27 and U79...

Defects in apoptotic programs contribute to a number of human diseases, ranging from neurodegenerative disorders to malignancy, and treatment failure. The genetic basis for apoptosis implies that cell death can be disrupted by mutations, raising the intriguing possibility that cell numbers can be regulated by factors that influence cell survival. It is well documented that the E2F1 transcriptio...

Nuclear receptors such as peroxisome proliferator-activated receptor α (PPARα) are potential therapeutic targets. In this study, we found that PPARα expression was lower in high grade gliomas and PPARα was an independent prognostic factor in GBM patients. PPARα agonism or overexpression inhibited glioma cell proliferation, invasion, and aerobic glycolysis as well as suppressed glioma growth in ...

Senescence limits cellular proliferation, and therefore might be a mechanism which could suppress the progression of cancer. Herein we show that E2F1, a transcription factor essential to a cell cycle progress and a main target of tumor suppressor Rb, is a critical barrier for the induction of senescence. Human cancer cells transfected with siE2F1 were shown to express replicative senescence mar...

Tumor necrosis factor-a (TNF-a) is expressed locally in the vessel wall after angioplasty and induces growth arrest and apoptosis in endothelial cells (ECs), thereby delaying reendothelialization. Prior studies have shown that direct antagonism of TNF-a, using a systemically administered soluble receptor, can enhance endothelial recovery and reduce neointimal thickening. These studies have also...

CDKN1C is a cyclin-dependent kinase inhibitor and is a candidate tumor suppressor gene. We previously found that the CDKN1C protein represses E2F1-driven transcription in an apparent negative feedback loop. Herein, we explore the mechanism by which CDKN1C represses transcription. We find that adenoviral-mediated overexpression of CDKN1C leads to a dramatic reduction in phosphorylation of the RN...

PURPOSE Receptor-interacting protein of 140 kDa (RIP140) is a transcriptional cofactor for nuclear receptors involved in reproduction and energy homeostasis. Our aim was to investigate its role in the regulation of E2F1 activity and target genes both in breast cancer cell lines and in tumor biopsies. EXPERIMENTAL DESIGN Glutathione S-transferase pull-down assays, coimmunoprecipitation experim...

Stem cell fate decisions are controlled by a molecular network in which transcription factors and miRNAs are of key importance. To systemically investigate their impact on neural stem cell (NSC) maintenance and neuronal commitment, we performed a high-throughput mRNA and miRNA profiling and isolated functional interaction networks of involved mechanisms. Thereby, we identified an E2F1-miRNA fee...