Search results for "E2F"
showing 7 items of 37 documents
The designer cytokine hyper-interleukin-6 is a potent activator of STAT3-dependent gene transcription in vivo and in vitro.
1999
Interleukin-6 (IL-6) triggers pivotal pathways in vivo. The designer protein hyper-IL-6 (H-IL-6) fuses the soluble IL-6 receptor (sIL-6R) through an intermediate linker with IL-6. The intracellular pathways that are triggered by H-IL-6 are not defined yet. Therefore, we studied the molecular mechanisms leading to H-IL-6-dependent gene activation. H-IL-6 stimulates haptoglobin mRNA expression in HepG2 cells, which is transcriptionally mediated as assessed by run-off experiments. The increase in haptoglobin gene transcription correlates with higher nuclear translocation of tyrosine-phosphorylated STAT3 and its DNA binding. As H-IL-6 stimulates STAT3-dependent gene transcription, we compared t…
Cellular Inhibitor of Apoptosis Protein-1 (cIAP1) Can Regulate E2F1 Transcription Factor-mediated Control of Cyclin Transcription
2011
International audience; The inhibitor of apoptosis protein cIAP1 (cellular inhibitor of apoptosis protein-1) is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-B signaling pathways in the cytoplasm. However, in some primary cells and tumor cell lines, cIAP1 is expressed in the nucleus, and its nuclear function remains poorly understood. Here, we show that the N-terminal part of cIAP1 directly interacts with the DNA binding domain of the E2F1 transcription factor. cIAP1 dramatically increases the transcriptional activity of E2F1 on synthetic and CCNE promoters. This function is not conserved for cIAP2 and XIAP, which are cytoplasmic proteins. Chromatin immunoprec…
Transcription, apoptosis and p53: catch-22
2005
The tumor suppressor p53 is a transcription factor and is activated in response to DNA damage or oncogenic transformation through modification of its interaction with regulatory proteins. The transcription factor activity of p53 is thought to mediate its primary functions of cell-cycle arrest and apoptosis through the gene expression it regulates, and evidence to support this interpretation continues to accumulate. However, reports of transcription-independent activities of p53, especially in the induction of apoptosis, persist. In particular, recent studies suggest that cytosolic p53 directly interacts with members of the BCL-2 family of apoptosis regulators, thereby triggering mitochondri…
The HMGA1 protoncogene frequently deregulated in cancer is a transcriptional target of E2F1
2011
Reactivation of the HMGA1 protoncogene is very frequent in human cancer, but still very little is known on the molecular mechanisms leading to this event. Prompted by the finding of putative E2F binding sites in the human HMGA1 promoter and by the frequent deregulation of the RB/E2F1 pathway in human carcinogenesis, we investigated whether E2F1 might contribute to the regulation of HMGA1 gene expression. Here we report that E2F1 induces HMGA1 by interacting with a 193bp region of the HMGA1 promoter containing an E2F binding site surrounded by three putative Sp1 binding sites. Both gain and loss of function experiments indicate that Sp1 functionally interacts with E2F1 to promote HMGA1 expre…
cIAP1 oncogenic properties analysis : contribution of its partners cdc42 and E2F1
2014
The inhibitor of apoptosis protein cIAP1 (cellular inhibitor of apoptosis protein-1) from the IAP family (Inhibitor of Apoptosis Protein) is an oncogene with an E3 ubiquitin ligase activity. cIAP1 is relocalized from the nucleus to the cytoplasm during the differentiation of many kind of cellular models (macrophages, dendritic cells, colon epithelial cells, hematopoietic stem cells, cardiomyocytes) and this relocalization is associated with a proliferation arrest. The well-known functions of cIAP1 are associated with its cytoplasmic localization, where it regulates the TNFa receptors and NF-?B signaling pathways. However, cIAP1 is mainly expressed in the nucleus on many cell types which is …
Analysis of E2F1 by clAP1
2017
The cellular inhibitor of Apoptosis 1 (cIAP1) behaves as an E3 ubiquitin ligase and has oncogenic properties. Previously, our team has shown that cIAP1 can regulate the E2F1 transcription factor activity. My research project has been focused on deepening our current knowledge on this interaction. Firstly, we characterized the E2F1-cIAP1 interaction, then we analyzed the regulation of E2F1 by cIAP1 and finally assessed the importance of the cIAP1-E2F1 interaction for the oncogenic properties of cIAP1. I have demonstrated a interaction of E2F1 with the hydrophobic pocket of the BIR3 domain of cIAP1. Moreover, I highlighted that the alpha 1 helix of the BIR3 domain is mandatory for the stabili…
Artemisinin–Second Career as Anticancer Drug?
2015
Artemisinin represents a showcase example not only for the activity of medicinal herbs deriving from traditional chinese medicine, but for phytotherapy in general. Its isolation from Sweet Wormwood (qinhao, Artemisia annua L.) represents the starting point for an unprecedent success story in the treatment of malaria worldwide. Beyond the therapeutic value against Plasmodium parasites, it turned out in recent years that the bioactivity of artemisinin is not restricted to malaria. We and others found that this sesquiterpenoid also exerts profound anticancer activity in vitro and in vivo. Artemisinin-type drugs exert multi-factorial cellular and molecular actions in cancer cells. Ferrous iron …