The Experts below are selected from a list of 2892 Experts worldwide ranked by ideXlab platform

Giyoung Kim - One of the best experts on this subject based on the ideXlab platform.

  • jnk inhibitor sp600125 promotes the formation of polymerized tubulin leading to g2 m phase arrest Endoreduplication and delayed apoptosis
    Experimental and Molecular Medicine, 2009
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Chang Hee Kang, Jaedong Lee, Giyoung Kim
    Abstract:

    The JNK inhibitor SP600125 strongly inhibits cell proliferation in many human cancer cells by blocking cell-cycle progression and inducing apoptosis. Despite extensive study, the mechanism by which SP600125 inhibits mitosis-related effects in human leukemia cells remains unclear. We investigated the effects of SP600125 on the inhibition of cell proliferation and the cell cycle, and on microtubule dynamics in vivo and in vitro. Treatment of synchronized leukemia cells with varying concentrations of SP600125 results in significant G2/M cell cycle arrest with elevated p21 levels, phosphorylation of histone H3 within 24 h, and Endoreduplication with elevated Cdk2 protein levels after 48 h. SP600125 also induces significant abnormal microtubule dynamics in vivo. High concentrations of SP600125 (200 µM) were required to disorganize microtubule polymerization in vitro. Additionally, SP600125-induced delayed apoptosis and cell death was accompanied by significant poly ADP-ribose polymerase (PARP) cleavage and caspase-3 activity in the late phase (at 72 h). Endoreduplication showed a greater increase in ectopic Bcl-2-expressing U937 cells at 72 h than in wild-type U937 cells without delayed apoptosis. These results indicate that Bcl-2 suppresses apoptosis and SP600125-induced G2/M arrest and Endoreduplication. Therefore, we suggest that SP600125 induces mitotic arrest by inducing abnormal spindle microtubule dynamics.

  • induction of g2 m arrest Endoreduplication and apoptosis by actin depolymerization agent pextenotoxin 2 in human leukemia cells involving activation of erk and jnk
    Biochemical Pharmacology, 2008
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Sanghyuck Kang, Kyeongjun Lee, Moonsoo Heo, Kwangsik Choi, Giyoung Kim
    Abstract:

    Pectenotoxin-2 (PTX-2) is a natural compound from marine sponges and has been known to inhibit cytokinesis through the depolymerization of actin filaments. To investigate the role of actin dysfunction by PTX-2 in human leukemia cells, we analyzed the effect of PTX-2 on the cell cycle and apoptosis. Cell cycle analysis showed that the depolymerization of actin with PTX-2 induces G2/M phase arrest at 12 h and Endoreduplication at 24 h. Analysis of the cell cycle regulatory proteins demonstrated that PTX-2 increases phosphorylation of cdc25c and decreases the protein levels of cdc2 and cyclin B1. The M phase specific marker protein, phospho-histone 3, was also increased by PTX-2. Furthermore, p21 and CDK2, which are associated with the induction of Endoreduplication, were also upregulated. PTX-2 also inhibited the growth of leukemia cells and caused a marked increase in apoptosis, as characterized by annexin-V+ cells and caspase-3 activity. Interestingly, we found that induction of G2/M phase arrest, Endoreduplication, and apoptosis by PTX-2 is regulated by the extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more increased the phosphorylation of cdc25c expression at G2/M arrest stages, and decreased p21 and CDK2 expression at Endoreduplication stages and Bax expression at apoptotic stages in the presence of PTX-2. These molecular mechanisms provide that PTX-2 induces G2/M phase arrest, Endoreduplication, and apoptosis through the ERK and JNK signal pathway via actin depolymerization.

  • β sitosterol induces g2 m arrest Endoreduplication and apoptosis through the bcl 2 and pi3k akt signaling pathways
    Cancer Letters, 2008
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Giyoung Kim
    Abstract:

    beta-Sitosterol (SITO) is a potentially valuable candidate for cancer chemotherapy, however the cellular and molecular mechanisms responsible for its anti-cancer activity are unknown. Therefore, we attempted to elucidate the mechanisms responsible for SITO-induced anti-proliferation in human leukemia cells. Treatment with SITO increased caspase-3 activation and DNA fragmentation in U937 and HL60 cells. This effect was associated with significant G2/M arrest and Endoreduplication. We also demonstrated that SITO treatment significantly increases levels of polymeric alpha-tubulin and promoted microtubule polymerization. We next elucidated that ectopic expression of Bcl-2 accelerates Endoreduplication in U937 cells. Furthermore, the specific Bcl-2 inhibitor, HA14-1, prevented Endoreduplication through G2 phase arrest. Interestingly, SITO treatment did not significantly promote Endoreduplication or decrease cell viability in Bcl-2 null K562 cells. SITO treatment also induced a gradual increase of phosphatidyl-inositol 3-kinase (PI3K) and Akt phosphorylation. Treatment with the selective PI3K/Akt inhibitor LY29004 completely blocked Endoreduplication and apoptosis in the presence of SITO. In addition, treatment with SITO-induced phosphorylation of extracellular signal-regulated protein kinase (ERK), however significance of ERK activation in the execution of apoptosis and Endoreduplication is unknown. These results suggest that SITO induces Endoreduplication by promoting spindle microtubule dynamics through the Bcl-2 and PI3K/Akt signaling pathways.

  • β sitosterol induces g2 m arrest Endoreduplication and apoptosis through the bcl 2 and pi3k akt signaling pathways
    Cancer Letters, 2008
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Giyoung Kim
    Abstract:

    Abstract β-Sitosterol (SITO) is a potentially valuable candidate for cancer chemotherapy, however the cellular and molecular mechanisms responsible for its anti-cancer activity are unknown. Therefore, we attempted to elucidate the mechanisms responsible for SITO-induced anti-proliferation in human leukemia cells. Treatment with SITO increased caspase-3 activation and DNA fragmentation in U937 and HL60 cells. This effect was associated with significant G 2 /M arrest and Endoreduplication. We also demonstrated that SITO treatment significantly increases levels of polymeric α-tubulin and promoted microtubule polymerization. We next elucidated that ectopic expression of Bcl-2 accelerates Endoreduplication in U937 cells. Furthermore, the specific Bcl-2 inhibitor, HA14-1, prevented Endoreduplication through G 2 phase arrest. Interestingly, SITO treatment did not significantly promote Endoreduplication or decrease cell viability in Bcl-2 null K562 cells. SITO treatment also induced a gradual increase of phosphatidyl-inositol 3-kinase (PI3K) and Akt phosphorylation. Treatment with the selective PI3K/Akt inhibitor LY29004 completely blocked Endoreduplication and apoptosis in the presence of SITO. In addition, treatment with SITO-induced phosphorylation of extracellular signal-regulated protein kinase (ERK), however significance of ERK activation in the execution of apoptosis and Endoreduplication is unknown. These results suggest that SITO induces Endoreduplication by promoting spindle microtubule dynamics through the Bcl-2 and PI3K/Akt signaling pathways.

Dongoh Moon - One of the best experts on this subject based on the ideXlab platform.

  • jnk inhibitor sp600125 promotes the formation of polymerized tubulin leading to g2 m phase arrest Endoreduplication and delayed apoptosis
    Experimental and Molecular Medicine, 2009
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Chang Hee Kang, Jaedong Lee, Giyoung Kim
    Abstract:

    The JNK inhibitor SP600125 strongly inhibits cell proliferation in many human cancer cells by blocking cell-cycle progression and inducing apoptosis. Despite extensive study, the mechanism by which SP600125 inhibits mitosis-related effects in human leukemia cells remains unclear. We investigated the effects of SP600125 on the inhibition of cell proliferation and the cell cycle, and on microtubule dynamics in vivo and in vitro. Treatment of synchronized leukemia cells with varying concentrations of SP600125 results in significant G2/M cell cycle arrest with elevated p21 levels, phosphorylation of histone H3 within 24 h, and Endoreduplication with elevated Cdk2 protein levels after 48 h. SP600125 also induces significant abnormal microtubule dynamics in vivo. High concentrations of SP600125 (200 µM) were required to disorganize microtubule polymerization in vitro. Additionally, SP600125-induced delayed apoptosis and cell death was accompanied by significant poly ADP-ribose polymerase (PARP) cleavage and caspase-3 activity in the late phase (at 72 h). Endoreduplication showed a greater increase in ectopic Bcl-2-expressing U937 cells at 72 h than in wild-type U937 cells without delayed apoptosis. These results indicate that Bcl-2 suppresses apoptosis and SP600125-induced G2/M arrest and Endoreduplication. Therefore, we suggest that SP600125 induces mitotic arrest by inducing abnormal spindle microtubule dynamics.

  • induction of g2 m arrest Endoreduplication and apoptosis by actin depolymerization agent pextenotoxin 2 in human leukemia cells involving activation of erk and jnk
    Biochemical Pharmacology, 2008
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Sanghyuck Kang, Kyeongjun Lee, Moonsoo Heo, Kwangsik Choi, Giyoung Kim
    Abstract:

    Pectenotoxin-2 (PTX-2) is a natural compound from marine sponges and has been known to inhibit cytokinesis through the depolymerization of actin filaments. To investigate the role of actin dysfunction by PTX-2 in human leukemia cells, we analyzed the effect of PTX-2 on the cell cycle and apoptosis. Cell cycle analysis showed that the depolymerization of actin with PTX-2 induces G2/M phase arrest at 12 h and Endoreduplication at 24 h. Analysis of the cell cycle regulatory proteins demonstrated that PTX-2 increases phosphorylation of cdc25c and decreases the protein levels of cdc2 and cyclin B1. The M phase specific marker protein, phospho-histone 3, was also increased by PTX-2. Furthermore, p21 and CDK2, which are associated with the induction of Endoreduplication, were also upregulated. PTX-2 also inhibited the growth of leukemia cells and caused a marked increase in apoptosis, as characterized by annexin-V+ cells and caspase-3 activity. Interestingly, we found that induction of G2/M phase arrest, Endoreduplication, and apoptosis by PTX-2 is regulated by the extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more increased the phosphorylation of cdc25c expression at G2/M arrest stages, and decreased p21 and CDK2 expression at Endoreduplication stages and Bax expression at apoptotic stages in the presence of PTX-2. These molecular mechanisms provide that PTX-2 induces G2/M phase arrest, Endoreduplication, and apoptosis through the ERK and JNK signal pathway via actin depolymerization.

  • β sitosterol induces g2 m arrest Endoreduplication and apoptosis through the bcl 2 and pi3k akt signaling pathways
    Cancer Letters, 2008
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Giyoung Kim
    Abstract:

    Abstract β-Sitosterol (SITO) is a potentially valuable candidate for cancer chemotherapy, however the cellular and molecular mechanisms responsible for its anti-cancer activity are unknown. Therefore, we attempted to elucidate the mechanisms responsible for SITO-induced anti-proliferation in human leukemia cells. Treatment with SITO increased caspase-3 activation and DNA fragmentation in U937 and HL60 cells. This effect was associated with significant G 2 /M arrest and Endoreduplication. We also demonstrated that SITO treatment significantly increases levels of polymeric α-tubulin and promoted microtubule polymerization. We next elucidated that ectopic expression of Bcl-2 accelerates Endoreduplication in U937 cells. Furthermore, the specific Bcl-2 inhibitor, HA14-1, prevented Endoreduplication through G 2 phase arrest. Interestingly, SITO treatment did not significantly promote Endoreduplication or decrease cell viability in Bcl-2 null K562 cells. SITO treatment also induced a gradual increase of phosphatidyl-inositol 3-kinase (PI3K) and Akt phosphorylation. Treatment with the selective PI3K/Akt inhibitor LY29004 completely blocked Endoreduplication and apoptosis in the presence of SITO. In addition, treatment with SITO-induced phosphorylation of extracellular signal-regulated protein kinase (ERK), however significance of ERK activation in the execution of apoptosis and Endoreduplication is unknown. These results suggest that SITO induces Endoreduplication by promoting spindle microtubule dynamics through the Bcl-2 and PI3K/Akt signaling pathways.

  • β sitosterol induces g2 m arrest Endoreduplication and apoptosis through the bcl 2 and pi3k akt signaling pathways
    Cancer Letters, 2008
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Giyoung Kim
    Abstract:

    beta-Sitosterol (SITO) is a potentially valuable candidate for cancer chemotherapy, however the cellular and molecular mechanisms responsible for its anti-cancer activity are unknown. Therefore, we attempted to elucidate the mechanisms responsible for SITO-induced anti-proliferation in human leukemia cells. Treatment with SITO increased caspase-3 activation and DNA fragmentation in U937 and HL60 cells. This effect was associated with significant G2/M arrest and Endoreduplication. We also demonstrated that SITO treatment significantly increases levels of polymeric alpha-tubulin and promoted microtubule polymerization. We next elucidated that ectopic expression of Bcl-2 accelerates Endoreduplication in U937 cells. Furthermore, the specific Bcl-2 inhibitor, HA14-1, prevented Endoreduplication through G2 phase arrest. Interestingly, SITO treatment did not significantly promote Endoreduplication or decrease cell viability in Bcl-2 null K562 cells. SITO treatment also induced a gradual increase of phosphatidyl-inositol 3-kinase (PI3K) and Akt phosphorylation. Treatment with the selective PI3K/Akt inhibitor LY29004 completely blocked Endoreduplication and apoptosis in the presence of SITO. In addition, treatment with SITO-induced phosphorylation of extracellular signal-regulated protein kinase (ERK), however significance of ERK activation in the execution of apoptosis and Endoreduplication is unknown. These results suggest that SITO induces Endoreduplication by promoting spindle microtubule dynamics through the Bcl-2 and PI3K/Akt signaling pathways.

  • β sitosterol induces g2 m arrest Endoreduplication and apoptosis through the bcl 2 and pi3k akt signaling pathways
    Clinical Cancer Research, 2007
    Co-Authors: Dongoh Moon, Yung Hyun Choi
    Abstract:

    B4 β-Sitosterol (SITO) is a potentially valuable candidate for cancer chemotherapy, however, the cellular and molecular mechanisms responsible for its anticancer activity are unknown. Therefore, we attempted to elucidate the mechanisms responsible for SITO-induced anti-proliferation in human leukemia cells. Treatment with SITOincreased caspase-3 activation and DNA fragmentation in U937 and HL60 cells. This effect was associated with significant G2/M arrest and Endoreduplication. We also demonstrated that SITO treatment significantly increases levels of polymeric α-tubulin and promoted microtubule polymerization. We next elucidated that ectopic expression of Bcl-2 accelerated Endoreduplication in U937 cells. Furthermore, the specific Bcl-2 inhibitor, HA14-1, prevented Endoreduplication through G2 phase arrest. Interestingly, SITO treatment did not promote Endoreduplication or decrease cell viability in Bcl-2 null K562 cells. SITO treatment also induced a gradual increase of PI3K and Akt phosphorylation. Treatment with the selective phosphatidyl-inositol 3-kinase (PI3K)/Akt inhibitor LY29004 completely blocked Endoreduplication and increased apoptosis in the presence of SITO. In addition, treatment with SITO induced phosphorylation of extracellular signal-regulated protein kinase (ERK), however, significance of ERK activation in the execution of apoptosis and Endoreduplication is unknown. These results suggest that SITO induces Endoreduplication by promoting spindle microtubule dynamics through the Bcl-2 and PI3K/Akt signaling pathways.

Yung Hyun Choi - One of the best experts on this subject based on the ideXlab platform.

  • jnk inhibitor sp600125 promotes the formation of polymerized tubulin leading to g2 m phase arrest Endoreduplication and delayed apoptosis
    Experimental and Molecular Medicine, 2009
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Chang Hee Kang, Jaedong Lee, Giyoung Kim
    Abstract:

    The JNK inhibitor SP600125 strongly inhibits cell proliferation in many human cancer cells by blocking cell-cycle progression and inducing apoptosis. Despite extensive study, the mechanism by which SP600125 inhibits mitosis-related effects in human leukemia cells remains unclear. We investigated the effects of SP600125 on the inhibition of cell proliferation and the cell cycle, and on microtubule dynamics in vivo and in vitro. Treatment of synchronized leukemia cells with varying concentrations of SP600125 results in significant G2/M cell cycle arrest with elevated p21 levels, phosphorylation of histone H3 within 24 h, and Endoreduplication with elevated Cdk2 protein levels after 48 h. SP600125 also induces significant abnormal microtubule dynamics in vivo. High concentrations of SP600125 (200 µM) were required to disorganize microtubule polymerization in vitro. Additionally, SP600125-induced delayed apoptosis and cell death was accompanied by significant poly ADP-ribose polymerase (PARP) cleavage and caspase-3 activity in the late phase (at 72 h). Endoreduplication showed a greater increase in ectopic Bcl-2-expressing U937 cells at 72 h than in wild-type U937 cells without delayed apoptosis. These results indicate that Bcl-2 suppresses apoptosis and SP600125-induced G2/M arrest and Endoreduplication. Therefore, we suggest that SP600125 induces mitotic arrest by inducing abnormal spindle microtubule dynamics.

  • induction of g2 m arrest Endoreduplication and apoptosis by actin depolymerization agent pextenotoxin 2 in human leukemia cells involving activation of erk and jnk
    Biochemical Pharmacology, 2008
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Sanghyuck Kang, Kyeongjun Lee, Moonsoo Heo, Kwangsik Choi, Giyoung Kim
    Abstract:

    Pectenotoxin-2 (PTX-2) is a natural compound from marine sponges and has been known to inhibit cytokinesis through the depolymerization of actin filaments. To investigate the role of actin dysfunction by PTX-2 in human leukemia cells, we analyzed the effect of PTX-2 on the cell cycle and apoptosis. Cell cycle analysis showed that the depolymerization of actin with PTX-2 induces G2/M phase arrest at 12 h and Endoreduplication at 24 h. Analysis of the cell cycle regulatory proteins demonstrated that PTX-2 increases phosphorylation of cdc25c and decreases the protein levels of cdc2 and cyclin B1. The M phase specific marker protein, phospho-histone 3, was also increased by PTX-2. Furthermore, p21 and CDK2, which are associated with the induction of Endoreduplication, were also upregulated. PTX-2 also inhibited the growth of leukemia cells and caused a marked increase in apoptosis, as characterized by annexin-V+ cells and caspase-3 activity. Interestingly, we found that induction of G2/M phase arrest, Endoreduplication, and apoptosis by PTX-2 is regulated by the extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more increased the phosphorylation of cdc25c expression at G2/M arrest stages, and decreased p21 and CDK2 expression at Endoreduplication stages and Bax expression at apoptotic stages in the presence of PTX-2. These molecular mechanisms provide that PTX-2 induces G2/M phase arrest, Endoreduplication, and apoptosis through the ERK and JNK signal pathway via actin depolymerization.

  • β sitosterol induces g2 m arrest Endoreduplication and apoptosis through the bcl 2 and pi3k akt signaling pathways
    Cancer Letters, 2008
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Giyoung Kim
    Abstract:

    Abstract β-Sitosterol (SITO) is a potentially valuable candidate for cancer chemotherapy, however the cellular and molecular mechanisms responsible for its anti-cancer activity are unknown. Therefore, we attempted to elucidate the mechanisms responsible for SITO-induced anti-proliferation in human leukemia cells. Treatment with SITO increased caspase-3 activation and DNA fragmentation in U937 and HL60 cells. This effect was associated with significant G 2 /M arrest and Endoreduplication. We also demonstrated that SITO treatment significantly increases levels of polymeric α-tubulin and promoted microtubule polymerization. We next elucidated that ectopic expression of Bcl-2 accelerates Endoreduplication in U937 cells. Furthermore, the specific Bcl-2 inhibitor, HA14-1, prevented Endoreduplication through G 2 phase arrest. Interestingly, SITO treatment did not significantly promote Endoreduplication or decrease cell viability in Bcl-2 null K562 cells. SITO treatment also induced a gradual increase of phosphatidyl-inositol 3-kinase (PI3K) and Akt phosphorylation. Treatment with the selective PI3K/Akt inhibitor LY29004 completely blocked Endoreduplication and apoptosis in the presence of SITO. In addition, treatment with SITO-induced phosphorylation of extracellular signal-regulated protein kinase (ERK), however significance of ERK activation in the execution of apoptosis and Endoreduplication is unknown. These results suggest that SITO induces Endoreduplication by promoting spindle microtubule dynamics through the Bcl-2 and PI3K/Akt signaling pathways.

  • β sitosterol induces g2 m arrest Endoreduplication and apoptosis through the bcl 2 and pi3k akt signaling pathways
    Cancer Letters, 2008
    Co-Authors: Dongoh Moon, Yung Hyun Choi, Munock Kim, Giyoung Kim
    Abstract:

    beta-Sitosterol (SITO) is a potentially valuable candidate for cancer chemotherapy, however the cellular and molecular mechanisms responsible for its anti-cancer activity are unknown. Therefore, we attempted to elucidate the mechanisms responsible for SITO-induced anti-proliferation in human leukemia cells. Treatment with SITO increased caspase-3 activation and DNA fragmentation in U937 and HL60 cells. This effect was associated with significant G2/M arrest and Endoreduplication. We also demonstrated that SITO treatment significantly increases levels of polymeric alpha-tubulin and promoted microtubule polymerization. We next elucidated that ectopic expression of Bcl-2 accelerates Endoreduplication in U937 cells. Furthermore, the specific Bcl-2 inhibitor, HA14-1, prevented Endoreduplication through G2 phase arrest. Interestingly, SITO treatment did not significantly promote Endoreduplication or decrease cell viability in Bcl-2 null K562 cells. SITO treatment also induced a gradual increase of phosphatidyl-inositol 3-kinase (PI3K) and Akt phosphorylation. Treatment with the selective PI3K/Akt inhibitor LY29004 completely blocked Endoreduplication and apoptosis in the presence of SITO. In addition, treatment with SITO-induced phosphorylation of extracellular signal-regulated protein kinase (ERK), however significance of ERK activation in the execution of apoptosis and Endoreduplication is unknown. These results suggest that SITO induces Endoreduplication by promoting spindle microtubule dynamics through the Bcl-2 and PI3K/Akt signaling pathways.

  • β sitosterol induces g2 m arrest Endoreduplication and apoptosis through the bcl 2 and pi3k akt signaling pathways
    Clinical Cancer Research, 2007
    Co-Authors: Dongoh Moon, Yung Hyun Choi
    Abstract:

    B4 β-Sitosterol (SITO) is a potentially valuable candidate for cancer chemotherapy, however, the cellular and molecular mechanisms responsible for its anticancer activity are unknown. Therefore, we attempted to elucidate the mechanisms responsible for SITO-induced anti-proliferation in human leukemia cells. Treatment with SITOincreased caspase-3 activation and DNA fragmentation in U937 and HL60 cells. This effect was associated with significant G2/M arrest and Endoreduplication. We also demonstrated that SITO treatment significantly increases levels of polymeric α-tubulin and promoted microtubule polymerization. We next elucidated that ectopic expression of Bcl-2 accelerated Endoreduplication in U937 cells. Furthermore, the specific Bcl-2 inhibitor, HA14-1, prevented Endoreduplication through G2 phase arrest. Interestingly, SITO treatment did not promote Endoreduplication or decrease cell viability in Bcl-2 null K562 cells. SITO treatment also induced a gradual increase of PI3K and Akt phosphorylation. Treatment with the selective phosphatidyl-inositol 3-kinase (PI3K)/Akt inhibitor LY29004 completely blocked Endoreduplication and increased apoptosis in the presence of SITO. In addition, treatment with SITO induced phosphorylation of extracellular signal-regulated protein kinase (ERK), however, significance of ERK activation in the execution of apoptosis and Endoreduplication is unknown. These results suggest that SITO induces Endoreduplication by promoting spindle microtubule dynamics through the Bcl-2 and PI3K/Akt signaling pathways.

Christian Chevalier - One of the best experts on this subject based on the ideXlab platform.

  • Endoreduplication and fruit growth in tomato: evidence in favour of the karyoplasmic ratio theory
    Journal of Experimental Botany, 2014
    Co-Authors: Christian Chevalier, Catherine Cheniclet, Frederic Gevaudant, Matthieu Bourdon, Julien Pirrello, Nathalie Frangne
    Abstract:

    The growth of a plant organ depends upon the developmental processes of cell division and cell expansion. The activity of cell divisions sets the number of cells that will make up the organ; the cell expansion activity then determines its final size. Among the various mechanisms that may influence the determination of cell size, endopolyploidy by means of Endoreduplication appears to be of great importance in plants. Endoreduplication is widespread in plants and supports the process of differentiation of cells and organs. Its functional role in plant cells is not fully understood, although it is commonly associated with ploidy-dependent cell expansion. During the development of tomato fruit, cells from the (fleshy) pericarp tissue become highly polyploid, reaching a DNA content barely encountered in other plant species (between 2C and 512C). Recent investigations using tomato fruit development as a model provided new data in favour of the long-standing karyoplasmic ratio theory, stating that cells tend to adjust their cytoplasmic volume to the nuclear DNA content. By establishing a highly structured cellular system where multiple physiological functions are integrated, Endoreduplication does act as a morphogenetic factor supporting cell growth during tomato fruit development.

  • The structural and molecular analysis of endoreduplicated nuclei in tomato (Solanum lycopersicum) fruit provides evidence for a ploidy-dependent increase in transcriptional activity
    Plant Biotechnology, 2013
    Co-Authors: Julien Pirrello, Catherine Cheniclet, Matthieu Bourdon, Nathalie Frangne, Jean-pierre Renaudin, Mickaël Bourge, Olivier Coriton, Spencer Brown, Christian Chevalier
    Abstract:

    Endopolyploidy, i.e. the amplification of genomic DNA without mitosis, is a widespread process in plants. Cells from the tomato fruit pericarp are characterized by a wide range of ploidy levels (from 2C to 256C). Although various functional hypotheses have been attributed to Endoreduplication according to the literature, evidence for a specific role of Endoreduplication in transcription and metabolism control is still lacking. We have developed a new method based on bacterial artificial chromosome fluorescent in situ hybridization (BAC-FISH) that allows the in situ determination of DNA ploidy levels of individual nuclei. The advantage of this method is illustrated by the analysis of ploidy levels and cell sizes within the pericarp tissue from mature green tomato fruits. Using this cellular approach we established the ploidy map of the pericarp tissue. Based on this map, we performed a structural analysis of endoreduplicated nuclei at the level of chromatin organization, nuclear shape and relationship with mitochondria. We demonstrated a link between the ploidy level of nuclei, the complexity of their shape and the number of mitochondria at the vicinity of polyploid nuclei. The use of the DNA FISH method demonstrated that endopolyploidy leads to the formation of polytene chromosomes, whereas the use of a RNA FISH method demonstrated that the rDNA transcription was increased during polyploidization. Performing quantitative PCR (qPCR) and RT-qPCR on sorted nuclei respectively, we confirmed that Endoreduplication did amplified exponentially loci for a set of specific genes allowing us to demonstrade that Endoreduplication results in an increasing transcriptional activity.

  • The specific overexpression of a cyclin-dependent kinase inhibitor in tomato fruit mesocarp cells uncouples Endoreduplication and cell growth
    Plant Journal, 2011
    Co-Authors: Mehdi Nafati, Catherine Cheniclet, Michel Hernould, Alisdair R. Fernie, Christian Chevalier, Frederic Gevaudant
    Abstract:

    The size of tomato fruit results from the combination of cell number and cell size, which are respectively determined by the cell division and cell expansion processes. As fruit growth is mainly sustained by cell expansion, the development of fleshy pericarp tissue is characterized by numerous rounds of Endoreduplication inducing a spectacular increase in DNA ploidy and mean cell size. Although a clear relationship exists between Endoreduplication and cell growth in plants, the exact role of Endoreduplication has not been clearly elucidated. To decipher the molecular basis of Endoreduplication-associated cell growth in fruit, we investigated the putative involvement of the tomato cyclin-dependent kinase inhibitor SlKRP1. We studied the kinetics of pericarp development in tomato fruit at the morphological and cytological levels, and demonstrated that Endoreduplication is directly proportional to cell and fruit diameter. We established a mathematical model for tissue growth according to the number of divisions and endocycles. This model was tested in fruits where we managed to decrease the extent of Endoreduplication by over-expressing SlKRP1 under the control of a fruit-specific promoter expressed during early development. Despite the fact that Endoreduplication was affected, we could not observe any morphological, cytological or metabolic phenotypes, indicating that determination of cell and fruit size can be, at least conditionally, uncoupled from Endoreduplication.

  • Elucidating the functional role of Endoreduplication in tomato fruit development
    Annals of Botany, 2011
    Co-Authors: Christian Chevalier, Mehdi Nafati, Catherine Cheniclet, Frederic Gevaudant, Elodie Mathieu-rivet, Matthieu Bourdon, Nathalie Frangne, Jean-pierre Renaudin, Michel Hernould
    Abstract:

    Background Endoreduplication is the major source of endopolyploidy in higher plants. The process of Endoreduplication results from the ability of cells to modify their classical cell cycle into a partial cell cycle where DNA synthesis occurs independently from mitosis. Despite the ubiquitous occurrence of the phenomenon in eukaryotic cells, the physiological meaning of Endoreduplication remains vague,although several roles during plant development have been proposed, mostly related to cell differentiation and cell size determination. Scope Here recent advances in the knowledge of Endoreduplication and fruit organogenesis are reviewed, focusing on tomato (Solanum lycopersicum) as a model, and the functional analyses of Endoreduplication-associated regulatory genes in tomato fruit are described. Conclusions The cyclin-dependent kinase inhibitory kinase WEE1 and the anaphase promoting complex activator CCS52A both participate in the control of cell size and the Endoreduplication process driving cell expansion during early fruit development in tomato. Moreover the fruit-specific functional analysis of the tomato CDK inhibitor KRP1 reveals that cell size and fruit size determination can be uncoupled from DNA ploidy levels, indicating that Endoreduplication acts rather as a limiting factor for cell growth. The overall functional data contribute to unravelling the physiological role of Endoreduplication in growth induction of fleshy fruits.

  • the cell cycle associated protein kinase wee1 regulates cell size in relation to Endoreduplication in developing tomato fruit
    Plant Journal, 2007
    Co-Authors: Nathalie Gonzalez, Michel Hernould, Christian Chevalier, Frederic Gevaudant, Armand Mouras
    Abstract:

    Tomato fruit size results from the combination of cell number and cell size which are respectively determined by cell division and cell expansion processes. As fruit growth is mainly sustained by cell expansion, the development of pericarp and locular tissues is characterized by the concomitant arrest of mitotic activity, inhibition of cyclin-dependent kinase (CDK) activity, and numerous rounds of Endoreduplication inducing a spectacular increase in DNA ploidy and mean cell size. To decipher the molecular basis of the Endoreduplication-associated cell growth in fruit, we investigated the putative involvement of the WEE1 kinase (Solly;WEE1). We here report a functional analysis of Solly;WEE1 in tomato. Impairing the expression of Solly;WEE1 in transgenic tomato plants resulted in a reduction of plant size and fruit size. In the most altered phenotypes, fruits displayed a reduced number of seeds without embryo development. The reduction of plant-, fruit- and seed size originated from a reduction in cell size which could be correlated with a decrease of the DNA ploidy levels. At the molecular level downregulating Solly;WEE1 in planta resulted in the increase of CDKA activity levels originating from a decrease of the amount of Y15-phosphorylated CDKA, thus indicating a release of the negative regulation on CDK activity exerted by WEE1. Our data indicated that Solly;WEE1 participates in the control of cell size and/or the onset of the Endoreduplication process putatively driving cell expansion.

Keiko Sugimotoshirasu - One of the best experts on this subject based on the ideXlab platform.

  • Endoreduplication and cell size control in plants
    eLS, 2007
    Co-Authors: Christian Breuer, Keiko Sugimotoshirasu
    Abstract:

    Endoreduplication involves replication of chromosomal deoxyribonucleic acid (DNA) without intervening mitoses. Endoreduplication and resulting high ploidy have often been correlated with an increase in cell size. Cell size is determined by highly dynamic, intersecting signalling pathways in plants, and the nuclear–cytoplasmic ratio is likely to provide a minimum constraint for this control. Keywords: Endoreduplication; cell-size control; cell growth; cell differentiation; cell cycle

  • rhl1 is an essential component of the plant dna topoisomerase vi complex and is required for ploidy dependent cell growth
    Proceedings of the National Academy of Sciences of the United States of America, 2005
    Co-Authors: Keiko Sugimotoshirasu, Nicola Stacey, Maureen C Mccann, Gethin R Roberts, Anthony Maxwell, Keith Roberts
    Abstract:

    How cells achieve their final sizes is a pervasive biological question. One strategy to increase cell size is for the cell to amplify its chromosomal DNA content through Endoreduplication cycles. Although Endoreduplication is widespread in eukaryotes, we know very little about its molecular mechanisms. Successful progression of the Endoreduplication cycle in Arabidopsis requires a plant homologue of archaeal DNA topoisomerase (topo) VI. To further understand how DNA is endoreduplicated and how this process is regulated, we isolated a dwarf Arabidopsis mutant, hyp7 (hypocotyl 7), in which various large cell types that in the wild type normally endoreduplicate multiple times complete only the first two rounds of Endoreduplication and stall at 8C. HYP7 encodes the RHL1 (ROOT HAIRLESS 1) protein, and sequence analysis reveals that RHL1 has similarity to the C-terminal domain of mammalian DNA topo IIα, another type II topo that shares little sequence homology with topo VI. RHL1 shows DNA binding activity in vitro, and we present both genetic and in vivo evidence that RHL1 forms a multiprotein complex with plant topo VI. We propose that RHL1 plays an essential role in the topo VI complex to modulate its function and that the two distantly related topos, topo II and topo VI, have evolved a common domain that extends their function. Our data suggest that plant topo II and topo VI play distinct but overlapping roles during the mitotic cell cycle and Endoreduplication cycle.

  • dna topoisomerase vi is essential for Endoreduplication in arabidopsis
    Current Biology, 2002
    Co-Authors: Keiko Sugimotoshirasu, Nicola Stacey, Julia Corsar, Keith Roberts, Maureen C Mccann
    Abstract:

    Abstract Endoreduplication is a common process in eukaryotes that involves DNA amplification without corresponding cell divisions. Cell size in various organisms has been linked to Endoreduplication [1, 2], but the molecular mechanisms are poorly understood. We have used a genetic strategy to identify molecules involved in endocycles in Arabidopsis . We isolated two extreme dwarf mutants, hypocotyl6 ( hyp6 ) and root hairless2 ( rhl2 ) [3], and cells of these mutants successfully complete only the first two rounds of Endoreduplication and stall at 8C. In both mutants, large cell types, such as trichomes [4, 5] and some epidermal cells [6], that normally endoreduplicate their DNA are much reduced in size. We show that HYP6 encodes AtTOP6B , a plant homolog of the archaeal DNA topoisomerase VI subunit B, and that RHL2 encodes AtSPO11-3 , one of the three Arabidopsis subunit A homologs. We propose that this topoisomerase VI complex is essential for the decatenation of replicated chromosomes during endocycles and that successive rounds of Endoreduplication are required for the full growth of specific cell types.