The Experts below are selected from a list of 98508 Experts worldwide ranked by ideXlab platform

Jean-luc Coll - One of the best experts on this subject based on the ideXlab platform.

Galina Merdzhanova - One of the best experts on this subject based on the ideXlab platform.

  • a new function of the splicing Factor srsf2 in the control of E2F1 mediated cell cycle progression in neuroendocrine lung tumors
    Cell Cycle, 2013
    Co-Authors: Valérie Edmond, Galina Merdzhanova, Stéphanie Gout, Sylvie Gazzeri, E Brambilla, Béatrice Eymin
    Abstract:

    The Transcription Factor E2F1 belongs to the E2F family and plays a crucial role during cell cycle progression and apoptosis. Ser/Arg-Rich (SR) proteins are a family of RNA-binding phosphoproteins that control both constitutive and alternative pre-mRNA splicing events. We previously identified the SR protein SRSF2 as a new Transcriptional target of E2F1 and demonstrated that both proteins cooperate to induce apoptosis in non-small cell lung carcinoma. In this study, we postulated that SRSF2 is also involved in the proliferative functions of E2F1. Using IHC, we first demonstrate that SRSF2 and its phosphorylated form (P-SRSF2) are overexpressed in neuroendocrine lung tumors that are highly proliferative tumors expressing high levels of E2F1. Importantly, we show a direct correlation between cyclin E, an E2F1-target gene controlling S phase, and P-SRSF2 proteins levels (p = 0.0083), suggesting a role of SRSF2 in E2F1-mediated cellular proliferation. Accordingly, using neuroendocrine lung carcinoma cell lines, we demonstrate that SRSF2 is a cell cycle-regulated protein involved in entry and progression into S phase. We also provide evidence that SRSF2 interacts with E2F1 and stimulates its Transcriptional control of cell cycle target genes such as cyclin E. Finally, we show that inhibition of AKT signaling pathway prevents SRSF2 phosphorylation and activity toward E2F1 Transcriptional function. Taken together, these results identify a new role of SRSF2 in the control of cell cycle progression and reinforce the functional link between SRSF2 and E2F1 proteins.

  • the Transcription Factor E2F1 and the sr protein sc35 control the ratio of pro angiogenic versus antiangiogenic isoforms of vascular endothelial growth Factor a to inhibit neovascularization in vivo
    Oncogene, 2010
    Co-Authors: Galina Merdzhanova, Stéphanie Gout, Michelle Keramidas, Valérie Edmond, Jean-luc Coll
    Abstract:

    The Transcription Factor E2F1 and the SR protein SC35 control the ratio of pro-angiogenic versus antiangiogenic isoforms of vascular endothelial growth Factor-A to inhibit neovascularization in vivo

  • the Transcription Factor E2F1 and the sr protein sc35 control the ratio of pro angiogenic versus antiangiogenic isoforms of vascular endothelial growth Factor a to inhibit neovascularization in vivo
    Oncogene, 2010
    Co-Authors: Galina Merdzhanova, Stéphanie Gout, Michelle Keramidas, Valérie Edmond, Jean-luc Coll, Christian Brambilla
    Abstract:

    The Transcription Factor E2F1 has a crucial role in the control of cell growth and has been shown to regulate neoangiogenesis in a p53-dependent manner through inhibition of activity of the VEGF-A (vascular endothelial growth Factor) promoter. Besides being regulated by Transcription, VEGF-A is also highly regulated by pre-mRNA alternative splicing, resulting in the expression of several VEGF isoforms with either pro-(VEGF(xxx)) or anti-(VEGF(xxx)b) angiogenic properties. Recently, we identified the SR (Ser-Rich/Arg) protein SC35, a splicing Factor, as a new Transcriptional target of E2F1. Here, we show that E2F1 downregulates the activity of the VEGF-A promoter in tumour cells independently of p53, leading to a strong decrease in VEGF(xxx) mRNA levels. We further show that, strikingly, E2F1 alters the ratio of pro-VEGF(xxx) versus anti-VEGF(xxx)b angiogenic isoforms, favouring the antiangiogenic isoforms, by a mechanism involving the induction of SC35 expression. Finally, using lung tumour xenografts in nude mice, we provide evidence that E2F1 and SC35 proteins increase the VEGF(165)b/VEGF ratio and decrease tumour neovascularization in vivo. Overall, these findings highlight E2F1 and SC35 as two regulators of the VEGF(xxx)/VEGF(xxx)b angiogenic switch in human cancer cells, a role that could be crucial during tumour progression, as well as in tumour response to antiangiogenic therapies.

  • E2F1 controls alternative splicing pattern of genes involved in apoptosis through upregulation of the splicing Factor SC35
    Cell Death & Differentiation, 2008
    Co-Authors: Galina Merdzhanova, Sylvie Gazzeri, V Edmond, S De Seranno, A Van Den Broeck, L Corcos, C Brambilla, E Brambilla, Béatrice Eymin
    Abstract:

    The Transcription Factor E2F1 has a key function during S phase progression and apoptosis. It has been well-demonstrated that the apoptotic function of E2F1 involves its ability to transactivate pro-apoptotic target genes. Alternative splicing of pre-mRNAs also has an important function in the regulation of apoptosis. In this study, we identify the splicing Factor SC35, a member of the Ser-Rich Arg (SR) proteins family, as a new Transcriptional target of E2F1. We demonstrate that E2F1 requires SC35 to switch the alternative splicing profile of various apoptotic genes such as c-flip , caspases-8 and - 9 and Bcl-x , towards the expression of pro-apoptotic splice variants. Finally, we provide evidence that E2F1 upregulates SC35 in response to DNA-damaging agents and show that SC35 is required for apoptosis in response to these drugs. Taken together, these results demonstrate that E2F1 controls pre-mRNA processing events to induce apoptosis and identify the SC35 SR protein as a key direct E2F1-target in this setting.

Valérie Edmond - One of the best experts on this subject based on the ideXlab platform.

  • a new function of the splicing Factor srsf2 in the control of E2F1 mediated cell cycle progression in neuroendocrine lung tumors
    Cell Cycle, 2013
    Co-Authors: Valérie Edmond, Galina Merdzhanova, Stéphanie Gout, Sylvie Gazzeri, E Brambilla, Béatrice Eymin
    Abstract:

    The Transcription Factor E2F1 belongs to the E2F family and plays a crucial role during cell cycle progression and apoptosis. Ser/Arg-Rich (SR) proteins are a family of RNA-binding phosphoproteins that control both constitutive and alternative pre-mRNA splicing events. We previously identified the SR protein SRSF2 as a new Transcriptional target of E2F1 and demonstrated that both proteins cooperate to induce apoptosis in non-small cell lung carcinoma. In this study, we postulated that SRSF2 is also involved in the proliferative functions of E2F1. Using IHC, we first demonstrate that SRSF2 and its phosphorylated form (P-SRSF2) are overexpressed in neuroendocrine lung tumors that are highly proliferative tumors expressing high levels of E2F1. Importantly, we show a direct correlation between cyclin E, an E2F1-target gene controlling S phase, and P-SRSF2 proteins levels (p = 0.0083), suggesting a role of SRSF2 in E2F1-mediated cellular proliferation. Accordingly, using neuroendocrine lung carcinoma cell lines, we demonstrate that SRSF2 is a cell cycle-regulated protein involved in entry and progression into S phase. We also provide evidence that SRSF2 interacts with E2F1 and stimulates its Transcriptional control of cell cycle target genes such as cyclin E. Finally, we show that inhibition of AKT signaling pathway prevents SRSF2 phosphorylation and activity toward E2F1 Transcriptional function. Taken together, these results identify a new role of SRSF2 in the control of cell cycle progression and reinforce the functional link between SRSF2 and E2F1 proteins.

  • the Transcription Factor E2F1 and the sr protein sc35 control the ratio of pro angiogenic versus antiangiogenic isoforms of vascular endothelial growth Factor a to inhibit neovascularization in vivo
    Oncogene, 2010
    Co-Authors: Galina Merdzhanova, Stéphanie Gout, Michelle Keramidas, Valérie Edmond, Jean-luc Coll
    Abstract:

    The Transcription Factor E2F1 and the SR protein SC35 control the ratio of pro-angiogenic versus antiangiogenic isoforms of vascular endothelial growth Factor-A to inhibit neovascularization in vivo

  • the Transcription Factor E2F1 and the sr protein sc35 control the ratio of pro angiogenic versus antiangiogenic isoforms of vascular endothelial growth Factor a to inhibit neovascularization in vivo
    Oncogene, 2010
    Co-Authors: Galina Merdzhanova, Stéphanie Gout, Michelle Keramidas, Valérie Edmond, Jean-luc Coll, Christian Brambilla
    Abstract:

    The Transcription Factor E2F1 has a crucial role in the control of cell growth and has been shown to regulate neoangiogenesis in a p53-dependent manner through inhibition of activity of the VEGF-A (vascular endothelial growth Factor) promoter. Besides being regulated by Transcription, VEGF-A is also highly regulated by pre-mRNA alternative splicing, resulting in the expression of several VEGF isoforms with either pro-(VEGF(xxx)) or anti-(VEGF(xxx)b) angiogenic properties. Recently, we identified the SR (Ser-Rich/Arg) protein SC35, a splicing Factor, as a new Transcriptional target of E2F1. Here, we show that E2F1 downregulates the activity of the VEGF-A promoter in tumour cells independently of p53, leading to a strong decrease in VEGF(xxx) mRNA levels. We further show that, strikingly, E2F1 alters the ratio of pro-VEGF(xxx) versus anti-VEGF(xxx)b angiogenic isoforms, favouring the antiangiogenic isoforms, by a mechanism involving the induction of SC35 expression. Finally, using lung tumour xenografts in nude mice, we provide evidence that E2F1 and SC35 proteins increase the VEGF(165)b/VEGF ratio and decrease tumour neovascularization in vivo. Overall, these findings highlight E2F1 and SC35 as two regulators of the VEGF(xxx)/VEGF(xxx)b angiogenic switch in human cancer cells, a role that could be crucial during tumour progression, as well as in tumour response to antiangiogenic therapies.

Stéphanie Gout - One of the best experts on this subject based on the ideXlab platform.

  • a new function of the splicing Factor srsf2 in the control of E2F1 mediated cell cycle progression in neuroendocrine lung tumors
    Cell Cycle, 2013
    Co-Authors: Valérie Edmond, Galina Merdzhanova, Stéphanie Gout, Sylvie Gazzeri, E Brambilla, Béatrice Eymin
    Abstract:

    The Transcription Factor E2F1 belongs to the E2F family and plays a crucial role during cell cycle progression and apoptosis. Ser/Arg-Rich (SR) proteins are a family of RNA-binding phosphoproteins that control both constitutive and alternative pre-mRNA splicing events. We previously identified the SR protein SRSF2 as a new Transcriptional target of E2F1 and demonstrated that both proteins cooperate to induce apoptosis in non-small cell lung carcinoma. In this study, we postulated that SRSF2 is also involved in the proliferative functions of E2F1. Using IHC, we first demonstrate that SRSF2 and its phosphorylated form (P-SRSF2) are overexpressed in neuroendocrine lung tumors that are highly proliferative tumors expressing high levels of E2F1. Importantly, we show a direct correlation between cyclin E, an E2F1-target gene controlling S phase, and P-SRSF2 proteins levels (p = 0.0083), suggesting a role of SRSF2 in E2F1-mediated cellular proliferation. Accordingly, using neuroendocrine lung carcinoma cell lines, we demonstrate that SRSF2 is a cell cycle-regulated protein involved in entry and progression into S phase. We also provide evidence that SRSF2 interacts with E2F1 and stimulates its Transcriptional control of cell cycle target genes such as cyclin E. Finally, we show that inhibition of AKT signaling pathway prevents SRSF2 phosphorylation and activity toward E2F1 Transcriptional function. Taken together, these results identify a new role of SRSF2 in the control of cell cycle progression and reinforce the functional link between SRSF2 and E2F1 proteins.

  • the Transcription Factor E2F1 and the sr protein sc35 control the ratio of pro angiogenic versus antiangiogenic isoforms of vascular endothelial growth Factor a to inhibit neovascularization in vivo
    Oncogene, 2010
    Co-Authors: Galina Merdzhanova, Stéphanie Gout, Michelle Keramidas, Valérie Edmond, Jean-luc Coll
    Abstract:

    The Transcription Factor E2F1 and the SR protein SC35 control the ratio of pro-angiogenic versus antiangiogenic isoforms of vascular endothelial growth Factor-A to inhibit neovascularization in vivo

  • the Transcription Factor E2F1 and the sr protein sc35 control the ratio of pro angiogenic versus antiangiogenic isoforms of vascular endothelial growth Factor a to inhibit neovascularization in vivo
    Oncogene, 2010
    Co-Authors: Galina Merdzhanova, Stéphanie Gout, Michelle Keramidas, Valérie Edmond, Jean-luc Coll, Christian Brambilla
    Abstract:

    The Transcription Factor E2F1 has a crucial role in the control of cell growth and has been shown to regulate neoangiogenesis in a p53-dependent manner through inhibition of activity of the VEGF-A (vascular endothelial growth Factor) promoter. Besides being regulated by Transcription, VEGF-A is also highly regulated by pre-mRNA alternative splicing, resulting in the expression of several VEGF isoforms with either pro-(VEGF(xxx)) or anti-(VEGF(xxx)b) angiogenic properties. Recently, we identified the SR (Ser-Rich/Arg) protein SC35, a splicing Factor, as a new Transcriptional target of E2F1. Here, we show that E2F1 downregulates the activity of the VEGF-A promoter in tumour cells independently of p53, leading to a strong decrease in VEGF(xxx) mRNA levels. We further show that, strikingly, E2F1 alters the ratio of pro-VEGF(xxx) versus anti-VEGF(xxx)b angiogenic isoforms, favouring the antiangiogenic isoforms, by a mechanism involving the induction of SC35 expression. Finally, using lung tumour xenografts in nude mice, we provide evidence that E2F1 and SC35 proteins increase the VEGF(165)b/VEGF ratio and decrease tumour neovascularization in vivo. Overall, these findings highlight E2F1 and SC35 as two regulators of the VEGF(xxx)/VEGF(xxx)b angiogenic switch in human cancer cells, a role that could be crucial during tumour progression, as well as in tumour response to antiangiogenic therapies.

Michelle Keramidas - One of the best experts on this subject based on the ideXlab platform.