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Raymond J Deshaies - One of the best experts on this subject based on the ideXlab platform.

  • multiple telophase arrest bypassed tab mutants alleviate the Essential Requirement for cdc15 in exit from mitosis in s cerevisiae
    BMC Genetics, 2002
    Co-Authors: Wenying Shou, Raymond J Deshaies
    Abstract:

    Background The Mitotic Exit Network (MEN) proteins – including the protein kinase Cdc15 and the protein phosphatase Cdc14 – are Essential for exit from mitosis in Saccharomyces cerevisiae. To identify downstream targets of the MEN, we sought telophase arrest bypassed (tab) mutations that bypassed the Essential Requirement for CDC15. Previous studies identified net1tab2-1 and CDC14TAB6-1 as mutations in the RENT complex subunits Net1 and Cdc14, respectively, and revealed that the MEN acts by promoting release of Cdc14 from its nucleolar Net1 anchor during anaphase. However, the remaining tab mutants were not characterized.

  • Multiple telophase arrest bypassed (tab) mutants alleviate the Essential Requirement for Cdc15 in exit from mitosis in S. cerevisiae
    BMC Genetics, 2002
    Co-Authors: Wenying Shou, Raymond J Deshaies
    Abstract:

    Background The Mitotic Exit Network (MEN) proteins – including the protein kinase Cdc15 and the protein phosphatase Cdc14 – are Essential for exit from mitosis in Saccharomyces cerevisiae. To identify downstream targets of the MEN, we sought telophase arrest bypassed (tab) mutations that bypassed the Essential Requirement for CDC15. Previous studies identified net1 ^ tab 2-1 and CDC14 ^ TAB 6-1 as mutations in the RENT complex subunits Net1 and Cdc14, respectively, and revealed that the MEN acts by promoting release of Cdc14 from its nucleolar Net1 anchor during anaphase. However, the remaining tab mutants were not characterized. Results Fourteen out of fifteen tab mutants were mapped to three recessive ( tab1-tab3 ) and three dominant ( TAB5-TAB7 ) linkage groups. We show that net1 ^ tab 2-1 enables growth of tem1Δ, cdc15Δ, dbf2Δ dbf20Δ, and mob1Δ, but not cdc5Δ or cdc14Δ, arguing that whereas the Essential task of the first four genes is to promote exit from mitosis, CDC5 possesses additional Essential function(s). net1 ^ tab 2-1 but not CDC14 ^ TAB 6-1 resulted in a high rate of chromosome loss, indicating that Net1 promotes accurate chromosome segregation in addition to its multiple known roles. Finally, TAB1 was shown to be MTR10, a gene encoding nuclear transport receptor/adaptor. In some of the tab mutants including mtr10 ^ tab 1-1, defective nuclear export of the ribosomal protein Rpl11b was observed. Furthermore, the transport-defective -31 allele of the karyopherin SRP1, but not the transport competent -49 allele, exhibited a tab phenotype. Conclusions Transport-defective mutations in two karyopherins can bypass cdc15Δ, suggesting that the function of the MEN is to promote mitotic exit by regulating nuclear transport.

  • multiple telophase arrest bypassed tab mutants alleviate the Essential Requirement for cdc15 in exit from mitosis in s cerevisiae
    BMC Genetics, 2002
    Co-Authors: Wenying Shou, Raymond J Deshaies
    Abstract:

    The Mitotic Exit Network (MEN) proteins – including the protein kinase Cdc15 and the protein phosphatase Cdc14 – are Essential for exit from mitosis in Saccharomyces cerevisiae. To identify downstream targets of the MEN, we sought telophase arrest bypassed (tab) mutations that bypassed the Essential Requirement for CDC15. Previous studies identified net1 tab2-1 and CDC14 TAB6-1 as mutations in the RENT complex subunits Net1 and Cdc14, respectively, and revealed that the MEN acts by promoting release of Cdc14 from its nucleolar Net1 anchor during anaphase. However, the remaining tab mutants were not characterized. Fourteen out of fifteen tab mutants were mapped to three recessive (tab1-tab3) and three dominant (TAB5-TAB7) linkage groups. We show that net1 tab2-1 enables growth of tem1Δ, cdc15Δ, dbf2Δ dbf20Δ, and mob1Δ, but not cdc5Δ or cdc14Δ, arguing that whereas the Essential task of the first four genes is to promote exit from mitosis, CDC5 possesses additional Essential function(s). net1 tab2-1 but not CDC14 TAB6-1 resulted in a high rate of chromosome loss, indicating that Net1 promotes accurate chromosome segregation in addition to its multiple known roles. Finally, TAB1 was shown to be MTR10, a gene encoding nuclear transport receptor/adaptor. In some of the tab mutants including mtr10 tab1-1, defective nuclear export of the ribosomal protein Rpl11b was observed. Furthermore, the transport-defective -31 allele of the karyopherin SRP1, but not the transport competent -49 allele, exhibited a tab phenotype. Transport-defective mutations in two karyopherins can bypass cdc15Δ, suggesting that the function of the MEN is to promote mitotic exit by regulating nuclear transport.

Dominique N Lisiero - One of the best experts on this subject based on the ideXlab platform.

  • an Essential Requirement for the scap srebp signaling axis to protect cancer cells from lipotoxicity
    Cancer Research, 2013
    Co-Authors: Kevin Jon Williams, Joseph P Argus, Moses Q Wilks, Autumn G York, Yoko Kidani, Alexandra L Pourzia, David Akhavan, Dominique N Lisiero, Beth N Marbois, Evangelia Komisopoulou
    Abstract:

    The sterol regulatory element-binding proteins (SREBP) are key transcriptional regulators of lipid metabolism and cellular growth. It has been proposed that SREBP signaling regulates cellular growth through its ability to drive lipid biosynthesis. Unexpectedly, we find that loss of SREBP activity inhibits cancer cell growth and viability by uncoupling fatty acid synthesis from desaturation. Integrated lipid profiling and metabolic flux analysis revealed that cancer cells with attenuated SREBP activity maintain long-chain saturated fatty acid synthesis, while losing fatty acid desaturation capacity. We traced this defect to the uncoupling of fatty acid synthase activity from stearoyl-CoA desaturase 1 (SCD1)–mediated desaturation. This deficiency in desaturation drives an imbalance between the saturated and monounsaturated fatty acid pools resulting in severe lipotoxicity. Importantly, replenishing the monounsaturated fatty acid pool restored growth to SREBP-inhibited cells. These studies highlight the importance of fatty acid desaturation in cancer growth and provide a novel mechanistic explanation for the role of SREBPs in cancer metabolism. Cancer Res; 73(9); 2850–62. ©2013 AACR .

  • an Essential Requirement for the scap srebp signaling axis to protect cancer cells from lipotoxicity
    Cancer Research, 2013
    Co-Authors: Kevin Jon Williams, Joseph P Argus, Moses Q Wilks, Autumn G York, Yoko Kidani, Alexandra L Pourzia, David Akhavan, Beth N Marbois, Yue Zhu, Dominique N Lisiero
    Abstract:

    The sterol regulatory element-binding proteins (SREBP) are key transcriptional regulators of lipid metabolism and cellular growth. It has been proposed that SREBP signaling regulates cellular growth through its ability to drive lipid biosynthesis. Unexpectedly, we find that loss of SREBP activity inhibits cancer cell growth and viability by uncoupling fatty acid synthesis from desaturation. Integrated lipid profiling and metabolic flux analysis revealed that cancer cells with attenuated SREBP activity maintain long-chain saturated fatty acid synthesis, while losing fatty acid desaturation capacity. We traced this defect to the uncoupling of fatty acid synthase activity from stearoyl-CoA desaturase 1 (SCD1)-mediated desaturation. This deficiency in desaturation drives an imbalance between the saturated and monounsaturated fatty acid pools resulting in severe lipotoxicity. Importantly, replenishing the monounsaturated fatty acid pool restored growth to SREBP-inhibited cells. These studies highlight the importance of fatty acid desaturation in cancer growth and provide a novel mechanistic explanation for the role of SREBPs in cancer metabolism.

Wenying Shou - One of the best experts on this subject based on the ideXlab platform.

  • multiple telophase arrest bypassed tab mutants alleviate the Essential Requirement for cdc15 in exit from mitosis in s cerevisiae
    BMC Genetics, 2002
    Co-Authors: Wenying Shou, Raymond J Deshaies
    Abstract:

    Background The Mitotic Exit Network (MEN) proteins – including the protein kinase Cdc15 and the protein phosphatase Cdc14 – are Essential for exit from mitosis in Saccharomyces cerevisiae. To identify downstream targets of the MEN, we sought telophase arrest bypassed (tab) mutations that bypassed the Essential Requirement for CDC15. Previous studies identified net1tab2-1 and CDC14TAB6-1 as mutations in the RENT complex subunits Net1 and Cdc14, respectively, and revealed that the MEN acts by promoting release of Cdc14 from its nucleolar Net1 anchor during anaphase. However, the remaining tab mutants were not characterized.

  • Multiple telophase arrest bypassed (tab) mutants alleviate the Essential Requirement for Cdc15 in exit from mitosis in S. cerevisiae
    BMC Genetics, 2002
    Co-Authors: Wenying Shou, Raymond J Deshaies
    Abstract:

    Background The Mitotic Exit Network (MEN) proteins – including the protein kinase Cdc15 and the protein phosphatase Cdc14 – are Essential for exit from mitosis in Saccharomyces cerevisiae. To identify downstream targets of the MEN, we sought telophase arrest bypassed (tab) mutations that bypassed the Essential Requirement for CDC15. Previous studies identified net1 ^ tab 2-1 and CDC14 ^ TAB 6-1 as mutations in the RENT complex subunits Net1 and Cdc14, respectively, and revealed that the MEN acts by promoting release of Cdc14 from its nucleolar Net1 anchor during anaphase. However, the remaining tab mutants were not characterized. Results Fourteen out of fifteen tab mutants were mapped to three recessive ( tab1-tab3 ) and three dominant ( TAB5-TAB7 ) linkage groups. We show that net1 ^ tab 2-1 enables growth of tem1Δ, cdc15Δ, dbf2Δ dbf20Δ, and mob1Δ, but not cdc5Δ or cdc14Δ, arguing that whereas the Essential task of the first four genes is to promote exit from mitosis, CDC5 possesses additional Essential function(s). net1 ^ tab 2-1 but not CDC14 ^ TAB 6-1 resulted in a high rate of chromosome loss, indicating that Net1 promotes accurate chromosome segregation in addition to its multiple known roles. Finally, TAB1 was shown to be MTR10, a gene encoding nuclear transport receptor/adaptor. In some of the tab mutants including mtr10 ^ tab 1-1, defective nuclear export of the ribosomal protein Rpl11b was observed. Furthermore, the transport-defective -31 allele of the karyopherin SRP1, but not the transport competent -49 allele, exhibited a tab phenotype. Conclusions Transport-defective mutations in two karyopherins can bypass cdc15Δ, suggesting that the function of the MEN is to promote mitotic exit by regulating nuclear transport.

  • multiple telophase arrest bypassed tab mutants alleviate the Essential Requirement for cdc15 in exit from mitosis in s cerevisiae
    BMC Genetics, 2002
    Co-Authors: Wenying Shou, Raymond J Deshaies
    Abstract:

    The Mitotic Exit Network (MEN) proteins – including the protein kinase Cdc15 and the protein phosphatase Cdc14 – are Essential for exit from mitosis in Saccharomyces cerevisiae. To identify downstream targets of the MEN, we sought telophase arrest bypassed (tab) mutations that bypassed the Essential Requirement for CDC15. Previous studies identified net1 tab2-1 and CDC14 TAB6-1 as mutations in the RENT complex subunits Net1 and Cdc14, respectively, and revealed that the MEN acts by promoting release of Cdc14 from its nucleolar Net1 anchor during anaphase. However, the remaining tab mutants were not characterized. Fourteen out of fifteen tab mutants were mapped to three recessive (tab1-tab3) and three dominant (TAB5-TAB7) linkage groups. We show that net1 tab2-1 enables growth of tem1Δ, cdc15Δ, dbf2Δ dbf20Δ, and mob1Δ, but not cdc5Δ or cdc14Δ, arguing that whereas the Essential task of the first four genes is to promote exit from mitosis, CDC5 possesses additional Essential function(s). net1 tab2-1 but not CDC14 TAB6-1 resulted in a high rate of chromosome loss, indicating that Net1 promotes accurate chromosome segregation in addition to its multiple known roles. Finally, TAB1 was shown to be MTR10, a gene encoding nuclear transport receptor/adaptor. In some of the tab mutants including mtr10 tab1-1, defective nuclear export of the ribosomal protein Rpl11b was observed. Furthermore, the transport-defective -31 allele of the karyopherin SRP1, but not the transport competent -49 allele, exhibited a tab phenotype. Transport-defective mutations in two karyopherins can bypass cdc15Δ, suggesting that the function of the MEN is to promote mitotic exit by regulating nuclear transport.

Kevin Jon Williams - One of the best experts on this subject based on the ideXlab platform.

  • an Essential Requirement for the scap srebp signaling axis to protect cancer cells from lipotoxicity
    Cancer Research, 2013
    Co-Authors: Kevin Jon Williams, Joseph P Argus, Moses Q Wilks, Autumn G York, Yoko Kidani, Alexandra L Pourzia, David Akhavan, Dominique N Lisiero, Beth N Marbois, Evangelia Komisopoulou
    Abstract:

    The sterol regulatory element-binding proteins (SREBP) are key transcriptional regulators of lipid metabolism and cellular growth. It has been proposed that SREBP signaling regulates cellular growth through its ability to drive lipid biosynthesis. Unexpectedly, we find that loss of SREBP activity inhibits cancer cell growth and viability by uncoupling fatty acid synthesis from desaturation. Integrated lipid profiling and metabolic flux analysis revealed that cancer cells with attenuated SREBP activity maintain long-chain saturated fatty acid synthesis, while losing fatty acid desaturation capacity. We traced this defect to the uncoupling of fatty acid synthase activity from stearoyl-CoA desaturase 1 (SCD1)–mediated desaturation. This deficiency in desaturation drives an imbalance between the saturated and monounsaturated fatty acid pools resulting in severe lipotoxicity. Importantly, replenishing the monounsaturated fatty acid pool restored growth to SREBP-inhibited cells. These studies highlight the importance of fatty acid desaturation in cancer growth and provide a novel mechanistic explanation for the role of SREBPs in cancer metabolism. Cancer Res; 73(9); 2850–62. ©2013 AACR .

  • an Essential Requirement for the scap srebp signaling axis to protect cancer cells from lipotoxicity
    Cancer Research, 2013
    Co-Authors: Kevin Jon Williams, Joseph P Argus, Moses Q Wilks, Autumn G York, Yoko Kidani, Alexandra L Pourzia, David Akhavan, Beth N Marbois, Yue Zhu, Dominique N Lisiero
    Abstract:

    The sterol regulatory element-binding proteins (SREBP) are key transcriptional regulators of lipid metabolism and cellular growth. It has been proposed that SREBP signaling regulates cellular growth through its ability to drive lipid biosynthesis. Unexpectedly, we find that loss of SREBP activity inhibits cancer cell growth and viability by uncoupling fatty acid synthesis from desaturation. Integrated lipid profiling and metabolic flux analysis revealed that cancer cells with attenuated SREBP activity maintain long-chain saturated fatty acid synthesis, while losing fatty acid desaturation capacity. We traced this defect to the uncoupling of fatty acid synthase activity from stearoyl-CoA desaturase 1 (SCD1)-mediated desaturation. This deficiency in desaturation drives an imbalance between the saturated and monounsaturated fatty acid pools resulting in severe lipotoxicity. Importantly, replenishing the monounsaturated fatty acid pool restored growth to SREBP-inhibited cells. These studies highlight the importance of fatty acid desaturation in cancer growth and provide a novel mechanistic explanation for the role of SREBPs in cancer metabolism.

Evangelia Komisopoulou - One of the best experts on this subject based on the ideXlab platform.

  • an Essential Requirement for the scap srebp signaling axis to protect cancer cells from lipotoxicity
    Cancer Research, 2013
    Co-Authors: Kevin Jon Williams, Joseph P Argus, Moses Q Wilks, Autumn G York, Yoko Kidani, Alexandra L Pourzia, David Akhavan, Dominique N Lisiero, Beth N Marbois, Evangelia Komisopoulou
    Abstract:

    The sterol regulatory element-binding proteins (SREBP) are key transcriptional regulators of lipid metabolism and cellular growth. It has been proposed that SREBP signaling regulates cellular growth through its ability to drive lipid biosynthesis. Unexpectedly, we find that loss of SREBP activity inhibits cancer cell growth and viability by uncoupling fatty acid synthesis from desaturation. Integrated lipid profiling and metabolic flux analysis revealed that cancer cells with attenuated SREBP activity maintain long-chain saturated fatty acid synthesis, while losing fatty acid desaturation capacity. We traced this defect to the uncoupling of fatty acid synthase activity from stearoyl-CoA desaturase 1 (SCD1)–mediated desaturation. This deficiency in desaturation drives an imbalance between the saturated and monounsaturated fatty acid pools resulting in severe lipotoxicity. Importantly, replenishing the monounsaturated fatty acid pool restored growth to SREBP-inhibited cells. These studies highlight the importance of fatty acid desaturation in cancer growth and provide a novel mechanistic explanation for the role of SREBPs in cancer metabolism. Cancer Res; 73(9); 2850–62. ©2013 AACR .