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B L Caputto - One of the best experts on this subject based on the ideXlab platform.
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The kinase c-Src and the phosphatase TC45 coordinately regulate C-Fos tyrosine phosphorylation and C-Fos phospholipid synthesis activation capacity
Oncogene, 2012Co-Authors: G O Ferrero, F N Velazquez, B L CaputtoAbstract:Our previous work showed that in T98G cells, a human glioblastoma multiforme-derived cell line, the association of C-Fos to the endoplasmic reticulum (ER) and consequently, the capacity of C-Fos to activate phospholipid synthesis, is regulated by the phosphorylation state of tyrosine (tyr) residues #10 and #30 of C-Fos. The small amount of C-Fos present in quiescent cells is tyr-phosphorylated, is dissociated from the ER membranes and does not activate phospholipid synthesis. However, on induction of the cell to re-enter growth, C-Fos expression is rapidly induced, it is found dephosphorylated, associated to ER membranes and activating phospholipid synthesis ( Portal et al., 2007 ). Herein, using in vivo and in vitro experimental strategies, we show that the kinase c-Src is capable of phosphorylating tyr residues of C-Fos whereas the phosphatase TC45 T-cell protein-tyr phosphatase (TC-PTP) dephosphorylates them, thus enabling C-Fos/ER association and activation of phospholipid synthesis. Results also suggest that the regulation of the phosphorylation/dephosphorylation cycle of C-Fos occurs at the TC-PTP level: induction of cells to re-enter growth promotes the translocation of TC45 from a nuclear to a cytoplasmic location concomitant with its activation. Activated TC45 in its turn promotes dephosphorylation of pre-formed C-Fos, enabling cells to rapidly activate phospholipid synthesis to respond to its growth demands.
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N-Terminal C-Fos tyrosine phosphorylation regulates C-Fos/ER association and C-Fos-dependent phospholipid synthesis activation
Oncogene, 2007Co-Authors: M M Portal, G O Ferrero, B L CaputtoAbstract:C-Fos dephosphorylated on tyrosine (C-Fos), a component of the activator protein-1 (AP-1) family of transcription factors, is expressed at very low levels in resting cells. However, its expression is rapidly upregulated in cells undergoing G_0 to S phase transition leading to AP-1-dependent gene transcription responses. In addition, cytoplasmic C-Fos associates to the endoplasmic reticulum (ER) membranes and activates phospholipid synthesis during cell growth and differentiation. Herein, it is shown that in T98G cells, C-Fos/ER association and consequently phospholipid synthesis activation is regulated by the phosphorylated state of C-Fos tyrosine (tyr) residues. The small amount of C-Fos present in quiescent T98G cells is tyr-phosphorylated and not ER-membrane bound. In growing cells, it is dephosphorylated, associated to ER membranes and promotes phospholipid synthesis activation. Impairing tyr-dephosphorylation abrogates phospholipid synthesis activation and reduces proliferation rates to those of quiescent cells. Substitution of tyr residues 10, 30, 106 and 337 evidence tyr 10 and 30 as relevant for this regulatory phenomenon. It is concluded that phosphorylation of tyr residues 10 and 30 of C-Fos regulate the rate of synthesis of phospholipids by regulating C-Fos/ER association.
Marc Piechaczyk - One of the best experts on this subject based on the ideXlab platform.
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down regulation of c fos c jun ap 1 dimer activity by sumoylation
Molecular and Cellular Biology, 2005Co-Authors: Guillaume Bossis, Cecile E Malnou, Rosa Farras, Elisabetta Andermarcher, Robert A Hipskind, Manuel S Rodriguez, Darja Schmidt, Stefan Muller, Isabelle Jarielencontre, Marc PiechaczykAbstract:The inducible transcriptional complex AP-1, composed of C-Fos and c-Jun proteins, is crucial for cell adaptation to many environmental changes. While its mechanisms of activation have been extensively studied, how its activity is restrained is poorly understood. We report here that lysine 265 of C-Fos is conjugated by the peptidic posttranslational modifiers SUMO-1, SUMO-2, and SUMO-3 and that c-Jun can be sumoylated on lysine 257 as well as on the previously described lysine 229. Sumoylation of C-Fos preferentially occurs in the context of c-Jun/C-Fos heterodimers. Using nonsumoylatable mutants of C-Fos and c-Jun as well as a chimeric protein mimicking sumoylated C-Fos, we show that sumoylation entails lower AP-1 transactivation activity. Interestingly, single sumoylation at any of the three acceptor sites of the C-Fos/c-Jun dimer is sufficient to substantially reduce transcription activation. The lower activity of sumoylated C-Fos is not due to inhibition of protein entry into the nucleus, accelerated turnover, and intrinsic inability to dimerize or to bind to DNA. Instead, cell fractionation experiments suggest that decreased transcriptional activity of sumoylated C-Fos is associated with specific intranuclear distribution. Interestingly, the phosphorylation of threonine 232 observed upon expression of oncogenically activated Ha-Ras is known to superactivate C-Fos transcriptional activity. We show here that it also inhibits C-Fos sumoylation, revealing a functional antagonism between two posttranslational modifications, each occurring within a different moiety of a bipartite transactivation domain of C-Fos. Finally we report that the sumoylation of C-Fos is a dynamic process that can be reversed via multiple mechanisms. This supports the idea that this modification does not constitute a final inactivation step that necessarily precedes protein degradation.
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Down-regulation of C-Fos/c-Jun AP-1 dimer activity by sumoylation
Molecular and Cellular Biology, 2005Co-Authors: Guillaume Bossis, Cecile E Malnou, Rosa Farras, Elisabetta Andermarcher, Robert A Hipskind, Darja Schmidt, Stefan Muller, M. Rodriguez, I. Jariel-encontre, Marc PiechaczykAbstract:The inducible transcriptional complex AP-1, composed of C-Fos and c-Jun proteins, is crucial for cell adaptation to many environmental changes. While its mechanisms of activation have been extensively studied, how its activity is restrained is poorly understood. We report here that lysine 265 of C-Fos is conjugated by the peptidic posttranslational modifiers SUMO-1, SUMO-2, and SUMO-3 and that c-Jun can be sumoylated on lysine 257 as well as on the previously described lysine 229. Sumoylation of C-Fos preferentially occurs in the context of c-Jun/C-Fos heterodimers. Using nonsumoylatable mutants of C-Fos and c-Jun as well as a chimeric protein mimicking sumoylated C-Fos, we show that sumoylation entails lower AP-1 transactivation activity. Interestingly, single sumoylation at any of the three acceptor sites of the C-Fos/c-Jun dimer is sufficient to substantially reduce transcription activation. The lower activity of sumoylated C-Fos is not due to inhibition of protein entry into the nucleus, accelerated turnover, and intrinsic inability to dimerize or to bind to DNA. Instead, cell fractionation experiments suggest that decreased transcriptional activity of sumoylated C-Fos is associated with specific intranuclear distribution. Interestingly, the phosphorylation of threonine 232 observed upon expression of oncogenically activated Ha-Ras is known to superactivate C-Fos transcriptional activity. We show here that it also inhibits C-Fos sumoylation, revealing a functional antagonism between two posttranslational modifications, each occurring within a different moiety of a bipartite transactivation domain of C-Fos. Finally we report that the sumoylation of C-Fos is a dynamic process that can be reversed via multiple mechanisms. This supports the idea that this modification does not constitute a final inactivation step that necessarily precedes protein degradation.
G O Ferrero - One of the best experts on this subject based on the ideXlab platform.
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The kinase c-Src and the phosphatase TC45 coordinately regulate C-Fos tyrosine phosphorylation and C-Fos phospholipid synthesis activation capacity
Oncogene, 2012Co-Authors: G O Ferrero, F N Velazquez, B L CaputtoAbstract:Our previous work showed that in T98G cells, a human glioblastoma multiforme-derived cell line, the association of C-Fos to the endoplasmic reticulum (ER) and consequently, the capacity of C-Fos to activate phospholipid synthesis, is regulated by the phosphorylation state of tyrosine (tyr) residues #10 and #30 of C-Fos. The small amount of C-Fos present in quiescent cells is tyr-phosphorylated, is dissociated from the ER membranes and does not activate phospholipid synthesis. However, on induction of the cell to re-enter growth, C-Fos expression is rapidly induced, it is found dephosphorylated, associated to ER membranes and activating phospholipid synthesis ( Portal et al., 2007 ). Herein, using in vivo and in vitro experimental strategies, we show that the kinase c-Src is capable of phosphorylating tyr residues of C-Fos whereas the phosphatase TC45 T-cell protein-tyr phosphatase (TC-PTP) dephosphorylates them, thus enabling C-Fos/ER association and activation of phospholipid synthesis. Results also suggest that the regulation of the phosphorylation/dephosphorylation cycle of C-Fos occurs at the TC-PTP level: induction of cells to re-enter growth promotes the translocation of TC45 from a nuclear to a cytoplasmic location concomitant with its activation. Activated TC45 in its turn promotes dephosphorylation of pre-formed C-Fos, enabling cells to rapidly activate phospholipid synthesis to respond to its growth demands.
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N-Terminal C-Fos tyrosine phosphorylation regulates C-Fos/ER association and C-Fos-dependent phospholipid synthesis activation
Oncogene, 2007Co-Authors: M M Portal, G O Ferrero, B L CaputtoAbstract:C-Fos dephosphorylated on tyrosine (C-Fos), a component of the activator protein-1 (AP-1) family of transcription factors, is expressed at very low levels in resting cells. However, its expression is rapidly upregulated in cells undergoing G_0 to S phase transition leading to AP-1-dependent gene transcription responses. In addition, cytoplasmic C-Fos associates to the endoplasmic reticulum (ER) membranes and activates phospholipid synthesis during cell growth and differentiation. Herein, it is shown that in T98G cells, C-Fos/ER association and consequently phospholipid synthesis activation is regulated by the phosphorylated state of C-Fos tyrosine (tyr) residues. The small amount of C-Fos present in quiescent T98G cells is tyr-phosphorylated and not ER-membrane bound. In growing cells, it is dephosphorylated, associated to ER membranes and promotes phospholipid synthesis activation. Impairing tyr-dephosphorylation abrogates phospholipid synthesis activation and reduces proliferation rates to those of quiescent cells. Substitution of tyr residues 10, 30, 106 and 337 evidence tyr 10 and 30 as relevant for this regulatory phenomenon. It is concluded that phosphorylation of tyr residues 10 and 30 of C-Fos regulate the rate of synthesis of phospholipids by regulating C-Fos/ER association.
Guillaume Bossis - One of the best experts on this subject based on the ideXlab platform.
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down regulation of c fos c jun ap 1 dimer activity by sumoylation
Molecular and Cellular Biology, 2005Co-Authors: Guillaume Bossis, Cecile E Malnou, Rosa Farras, Elisabetta Andermarcher, Robert A Hipskind, Manuel S Rodriguez, Darja Schmidt, Stefan Muller, Isabelle Jarielencontre, Marc PiechaczykAbstract:The inducible transcriptional complex AP-1, composed of C-Fos and c-Jun proteins, is crucial for cell adaptation to many environmental changes. While its mechanisms of activation have been extensively studied, how its activity is restrained is poorly understood. We report here that lysine 265 of C-Fos is conjugated by the peptidic posttranslational modifiers SUMO-1, SUMO-2, and SUMO-3 and that c-Jun can be sumoylated on lysine 257 as well as on the previously described lysine 229. Sumoylation of C-Fos preferentially occurs in the context of c-Jun/C-Fos heterodimers. Using nonsumoylatable mutants of C-Fos and c-Jun as well as a chimeric protein mimicking sumoylated C-Fos, we show that sumoylation entails lower AP-1 transactivation activity. Interestingly, single sumoylation at any of the three acceptor sites of the C-Fos/c-Jun dimer is sufficient to substantially reduce transcription activation. The lower activity of sumoylated C-Fos is not due to inhibition of protein entry into the nucleus, accelerated turnover, and intrinsic inability to dimerize or to bind to DNA. Instead, cell fractionation experiments suggest that decreased transcriptional activity of sumoylated C-Fos is associated with specific intranuclear distribution. Interestingly, the phosphorylation of threonine 232 observed upon expression of oncogenically activated Ha-Ras is known to superactivate C-Fos transcriptional activity. We show here that it also inhibits C-Fos sumoylation, revealing a functional antagonism between two posttranslational modifications, each occurring within a different moiety of a bipartite transactivation domain of C-Fos. Finally we report that the sumoylation of C-Fos is a dynamic process that can be reversed via multiple mechanisms. This supports the idea that this modification does not constitute a final inactivation step that necessarily precedes protein degradation.
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Down-regulation of C-Fos/c-Jun AP-1 dimer activity by sumoylation
Molecular and Cellular Biology, 2005Co-Authors: Guillaume Bossis, Cecile E Malnou, Rosa Farras, Elisabetta Andermarcher, Robert A Hipskind, Darja Schmidt, Stefan Muller, M. Rodriguez, I. Jariel-encontre, Marc PiechaczykAbstract:The inducible transcriptional complex AP-1, composed of C-Fos and c-Jun proteins, is crucial for cell adaptation to many environmental changes. While its mechanisms of activation have been extensively studied, how its activity is restrained is poorly understood. We report here that lysine 265 of C-Fos is conjugated by the peptidic posttranslational modifiers SUMO-1, SUMO-2, and SUMO-3 and that c-Jun can be sumoylated on lysine 257 as well as on the previously described lysine 229. Sumoylation of C-Fos preferentially occurs in the context of c-Jun/C-Fos heterodimers. Using nonsumoylatable mutants of C-Fos and c-Jun as well as a chimeric protein mimicking sumoylated C-Fos, we show that sumoylation entails lower AP-1 transactivation activity. Interestingly, single sumoylation at any of the three acceptor sites of the C-Fos/c-Jun dimer is sufficient to substantially reduce transcription activation. The lower activity of sumoylated C-Fos is not due to inhibition of protein entry into the nucleus, accelerated turnover, and intrinsic inability to dimerize or to bind to DNA. Instead, cell fractionation experiments suggest that decreased transcriptional activity of sumoylated C-Fos is associated with specific intranuclear distribution. Interestingly, the phosphorylation of threonine 232 observed upon expression of oncogenically activated Ha-Ras is known to superactivate C-Fos transcriptional activity. We show here that it also inhibits C-Fos sumoylation, revealing a functional antagonism between two posttranslational modifications, each occurring within a different moiety of a bipartite transactivation domain of C-Fos. Finally we report that the sumoylation of C-Fos is a dynamic process that can be reversed via multiple mechanisms. This supports the idea that this modification does not constitute a final inactivation step that necessarily precedes protein degradation.
Leiriane Sangama Mesquita - One of the best experts on this subject based on the ideXlab platform.
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educacao ambiental sobre os botos da amazonia sotalia fluviatilis e inia geoffrensis mammalia cetacea uma proposta de orientacao a pescadores em atalaia do norte am
2009Co-Authors: Leiriane Sangama MesquitaAbstract:Nas aguas amazonicas coexistem duas especies de cetaceos, o boto tucuxi (Sotalia fluviatilis GERVAIS & DEVILLE, 1853) da familia Delphinidae, e o boto-vermelho (Inia geoffrensis BLAINVILE, 1817) da familia Iniidae. Para se alimentar, podem competir com as frotas pesqueiras em comunidades ribeirinhas, o que muitas vezes culmina com o emalhe destes animais nas redes de pesca, evento conhecido como captura acidental. Outro aspecto a se considerar sao as lendas folcloricas oriundas da cultura ribeirinha ou indigena, que fazem parte do imaginario dos pescadores. Alem disso, por vezes, e manifestada certa antipatia por parte dos pescadores em relacao a estes animais, ja que os mesmos ocasionalmente rasgam suas redes de pesca. Visando a sensibilizacao da comunidade pesqueira do municipio de Atalaia do Norte quanto a relevância ambiental destas especies e ainda avaliar o impacto da atividade de educacao ambiental proposta, sera realizado o cadastramento dos pescadores artesanais do municipio de Atalaia do Norte, aos quais serao aplicados questionarios sobre aspectos relacionados a interacao botos-pesca. Serao realizadas palestras educacionais ressaltando a importância da preservacao do boto tucuxi e do boto vermelho direcionadas aos pescadores. Posteriormente, sera avaliado o impacto das palestras sobre a interpretacao dos pescadores, verificando a eficacia da acao proposta.
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Educação ambiental sobre os botos da Amazônia (Sotalia fluviatilis e Inia geoffrensis MAMMALIA, CETACEA): Uma proposta de orientação a pescadores em Atalaia do Norte Am.
UFAM, 2009Co-Authors: Leiriane Sangama MesquitaAbstract:Nas águas amazônicas coexistem duas espécies de cetáceos, o boto tucuxi (Sotalia fluviatilis GERVAIS & DEVILLE, 1853) da família Delphinidae, e o boto-vermelho (Inia geoffrensis BLAINVILE, 1817) da família Iniidae. Para se alimentar, podem competir com as frotas pesqueiras em comunidades ribeirinhas, o que muitas vezes culmina com o emalhe destes animais nas redes de pesca, evento conhecido como captura acidental. Outro aspecto a se considerar são as lendas folclóricas oriundas da cultura ribeirinha ou indígena, que fazem parte do imaginário dos pescadores. Além disso, por vezes, é manifestada certa antipatia por parte dos pescadores em relação a estes animais, já que os mesmos ocasionalmente rasgam suas redes de pesca. Visando à sensibilização da comunidade pesqueira do município de Atalaia do Norte quanto à relevância ambiental destas espécies e ainda avaliar o impacto da atividade de educação ambiental proposta, será realizado o cadastramento dos pescadores artesanais do município de Atalaia do Norte, aos quais serão aplicados questionários sobre aspectos relacionados à interação botos-pesca. Serão realizadas palestras educacionais ressaltando a importância da preservação do boto tucuxi e do boto vermelho direcionadas aos pescadores. Posteriormente, será avaliado o impacto das palestras sobre a interpretação dos pescadores, verificando a eficácia da ação proposta.FAPEA
