As a cell cycle regulator, the Myb-related CDC5 protein was reported to be essential for the G2 phase of the cell cycle in yeast and animals, but little is known about its function in plants. Here we report the functi...As a cell cycle regulator, the Myb-related CDC5 protein was reported to be essential for the G2 phase of the cell cycle in yeast and animals, but little is known about its function in plants. Here we report the functional characterization of the CDC5 gene in Arabidopsis thaliana. Arabidopsis CDC5 （AtCDC5） is mainly expressed in tissues with high cell division activity, and is expressed throughout the entire process of embryo formation. The AtCDC5 loss-of-function mutant is embryonic lethal. In order to investigate the function of AtCDC5 in vivo, we generated AtCDC5-RNAi plants in which the expression of AtCDC5 was reduced by RNA interference. We found that the G2 to M （G2/M） phase transition was affected in the AtCDC5-RNAi plants, and that endoreduplication was increased. Additionally, the maintenance of shoot apical meristem （SAM） function was disturbed in the AtCDC5-RNAi plants, in which both the WUSCHEL （WUS）- CLAVATA （CLV） and the SHOOT MERISTEMLESS （STM） pathways were impaired. In situ hybridization analysis showed that the expression of STMwas greatly reduced in the shoot apical cells of the AtCDC5-RNAi plants. Moreover, cyclinB1 or Histone4 was found to be expressed in some of these cells when the transcript of STM was undetectable. These results suggest that AtCDC5 is essential for the G2/M phase transition and may regulate the function of SAM by controlling the expression ofSTMand WUS.展开更多
Cancer cells show characteristic alterations in DNA methylation patterns. Aberrant CpG methylation of specificpromoters results in inactivation of tumor suppressor genes and therefore plays an important role in carcin...Cancer cells show characteristic alterations in DNA methylation patterns. Aberrant CpG methylation of specificpromoters results in inactivation of tumor suppressor genes and therefore plays an important role in carcinogenesis. Thep53-regulated gene 14-3-3σ undergoes frequent epigenetic silencing in several types of cancer, including carcinoma ofthe breast, prostate, and skin, suggesting that the loss of 14-3-3σ expression may be causally involved in tumor progression.Functional studies demonstrated that 14-3-3σ is involved in cell-cycle control and prevents the accumulation of chro-mosomal damage. The recent identification of novel 14-3-3σ-associated proteins by a targeted proteomics approachimplies that 14-3-3σ regulates diverse cellular processes, which may become deregulated after silencing of 14-3-3σexpression in cancer cells.展开更多
Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein with a unique structural fold. Despite the fact that HABP1 possesses mitochondrial localization signal, it has also been l...Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein with a unique structural fold. Despite the fact that HABP1 possesses mitochondrial localization signal, it has also been localized to other cellular compartments. Using indirect immunofluorescence, we examined the sub-cellular localization of HABP1 and its dynamics during mitosis. We wanted to determine whether it distributes in any distinctive manner after mitotic nuclear envelope disassembly or is dispersed randomly throughout the cell. Our results reveal the golgi localization of HABP1 and demonstrate its complete dispersion throughout the cell during mitosis. This distinctive distribution pattern of HABP1 during mitosis resembles its ligand hyaluronan, suggesting that in concert with each other the two molecules play critical roles in this dynamic process.展开更多
AIM: Fatty acid-CoA ligase 4 (FACL4) is an arachidonatepreferring enzyme which has been shown to be up-regulated in human colon cancer tissues and implicated in the colon tumorigenesis. The purpose of this study was t...AIM: Fatty acid-CoA ligase 4 (FACL4) is an arachidonatepreferring enzyme which has been shown to be up-regulated in human colon cancer tissues and implicated in the colon tumorigenesis. The purpose of this study was to investigatethe role of FACL4 in the human hepatocellular carcinoma (HCC) tumorigenesis and the specific signal pathways involved in this process.METHODS: We investigated the expression and regulation of FACL4 in HCC, adjacent non-tumorous liver tissues, and cell lines.RESULTS: In HCC patients, we demonstrated that FACL4 gene expression was markedly elevated in the cancerous tissues than in the adjacent non-cancerous liver tissues.In addition, several human hepatoma cell lines, including Hep3B and HepG2, expressed high levels of FACL4. Stable overex-pression of FACL4 knockdown plasmids (small interfering RNA, siRNA) to Hep3B cells significantly decreased FACL4 expression and subsequently limited the cell proliferation. Treatment of Hep3B cells with 8bromo-cAMP and SB203508 (p38 MAPK inhibitor) significantly suppressed the FACL4 expression. CONCLUSION: FACL4 is involved in the HCC tumorigenesis and both cAMP and p38 MAPK pathways are associated with the regulation of FACL4 in HCC.展开更多
Hepatitis B virus X protein （HBx） plays a crucial role in the development of hepatocellular carcinoma. Here, we sought to identify the mechanisms by which HBx mediates liver cell proliferation. We found that HBx upr...Hepatitis B virus X protein （HBx） plays a crucial role in the development of hepatocellular carcinoma. Here, we sought to identify the mechanisms by which HBx mediates liver cell proliferation. We found that HBx upregulated the levels of cyclooxygenase-2 （COX-2）, 5-1ipoxygenase （5-LOX） and phosphorylated extracellular signal-regulated protein kinases 1/2 （p-ERK1/2） in liver cells. HBx-induced p-ERK1/2 was abolished by inhibition of Gi/o proteins, COX or LOX. In addition, HBx increased the amounts of prostaglandin E2 （PGE2） and leukotriene B4 （LTB4） released from cell lines derived from hepatocytes. Moreover, these released arachidonic acid metabolites were able to activate ERK1/2. Interestingly, activated ERK1/2 could upregulate the expression of COX-2 and 5-LOX in a positive feedback manner. In conclusion, HBx enhances and maintains liver cell proliferation via a positive feedback loop involving COX-2, 5-LOX, released arachidonic acid metabolites, Gi/o proteins and p-ERK1/2.展开更多
基金Acknowledgments The authors thank Dr Liying Du （Peking University, China） for technical help on the flow cytometric analysis. The authors also thank Dr Zhongchi Liu （University of Maryland, USA）, Dr Chun-Ming Liu （Institute of Botany CAS, China）, Dr Terry Matthew （University of Southampton, UK）, Professor Daochun Kong （Peking University, China） and Dr Naomi Nakayama （Yale University, USA） for critical comments and valuable discussion. This work was supported by the National Natural Science Foundation of China （GN 30625002 to L-J Qu）.
文摘As a cell cycle regulator, the Myb-related CDC5 protein was reported to be essential for the G2 phase of the cell cycle in yeast and animals, but little is known about its function in plants. Here we report the functional characterization of the CDC5 gene in Arabidopsis thaliana. Arabidopsis CDC5 （AtCDC5） is mainly expressed in tissues with high cell division activity, and is expressed throughout the entire process of embryo formation. The AtCDC5 loss-of-function mutant is embryonic lethal. In order to investigate the function of AtCDC5 in vivo, we generated AtCDC5-RNAi plants in which the expression of AtCDC5 was reduced by RNA interference. We found that the G2 to M （G2/M） phase transition was affected in the AtCDC5-RNAi plants, and that endoreduplication was increased. Additionally, the maintenance of shoot apical meristem （SAM） function was disturbed in the AtCDC5-RNAi plants, in which both the WUSCHEL （WUS）- CLAVATA （CLV） and the SHOOT MERISTEMLESS （STM） pathways were impaired. In situ hybridization analysis showed that the expression of STMwas greatly reduced in the shoot apical cells of the AtCDC5-RNAi plants. Moreover, cyclinB1 or Histone4 was found to be expressed in some of these cells when the transcript of STM was undetectable. These results suggest that AtCDC5 is essential for the G2/M phase transition and may regulate the function of SAM by controlling the expression ofSTMand WUS.
文摘Cancer cells show characteristic alterations in DNA methylation patterns. Aberrant CpG methylation of specificpromoters results in inactivation of tumor suppressor genes and therefore plays an important role in carcinogenesis. Thep53-regulated gene 14-3-3σ undergoes frequent epigenetic silencing in several types of cancer, including carcinoma ofthe breast, prostate, and skin, suggesting that the loss of 14-3-3σ expression may be causally involved in tumor progression.Functional studies demonstrated that 14-3-3σ is involved in cell-cycle control and prevents the accumulation of chro-mosomal damage. The recent identification of novel 14-3-3σ-associated proteins by a targeted proteomics approachimplies that 14-3-3σ regulates diverse cellular processes, which may become deregulated after silencing of 14-3-3σexpression in cancer cells.
文摘Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein with a unique structural fold. Despite the fact that HABP1 possesses mitochondrial localization signal, it has also been localized to other cellular compartments. Using indirect immunofluorescence, we examined the sub-cellular localization of HABP1 and its dynamics during mitosis. We wanted to determine whether it distributes in any distinctive manner after mitotic nuclear envelope disassembly or is dispersed randomly throughout the cell. Our results reveal the golgi localization of HABP1 and demonstrate its complete dispersion throughout the cell during mitosis. This distinctive distribution pattern of HABP1 during mitosis resembles its ligand hyaluronan, suggesting that in concert with each other the two molecules play critical roles in this dynamic process.
基金Supported by the National Science Council of Taiwan Chna(NSC 91-2320-B-038-030- and 92-2320-B-038-051-)Taipei Medical University (TMU 91-Y05-A138)
文摘AIM: Fatty acid-CoA ligase 4 (FACL4) is an arachidonatepreferring enzyme which has been shown to be up-regulated in human colon cancer tissues and implicated in the colon tumorigenesis. The purpose of this study was to investigatethe role of FACL4 in the human hepatocellular carcinoma (HCC) tumorigenesis and the specific signal pathways involved in this process.METHODS: We investigated the expression and regulation of FACL4 in HCC, adjacent non-tumorous liver tissues, and cell lines.RESULTS: In HCC patients, we demonstrated that FACL4 gene expression was markedly elevated in the cancerous tissues than in the adjacent non-cancerous liver tissues.In addition, several human hepatoma cell lines, including Hep3B and HepG2, expressed high levels of FACL4. Stable overex-pression of FACL4 knockdown plasmids (small interfering RNA, siRNA) to Hep3B cells significantly decreased FACL4 expression and subsequently limited the cell proliferation. Treatment of Hep3B cells with 8bromo-cAMP and SB203508 (p38 MAPK inhibitor) significantly suppressed the FACL4 expression. CONCLUSION: FACL4 is involved in the HCC tumorigenesis and both cAMP and p38 MAPK pathways are associated with the regulation of FACL4 in HCC.
文摘Hepatitis B virus X protein （HBx） plays a crucial role in the development of hepatocellular carcinoma. Here, we sought to identify the mechanisms by which HBx mediates liver cell proliferation. We found that HBx upregulated the levels of cyclooxygenase-2 （COX-2）, 5-1ipoxygenase （5-LOX） and phosphorylated extracellular signal-regulated protein kinases 1/2 （p-ERK1/2） in liver cells. HBx-induced p-ERK1/2 was abolished by inhibition of Gi/o proteins, COX or LOX. In addition, HBx increased the amounts of prostaglandin E2 （PGE2） and leukotriene B4 （LTB4） released from cell lines derived from hepatocytes. Moreover, these released arachidonic acid metabolites were able to activate ERK1/2. Interestingly, activated ERK1/2 could upregulate the expression of COX-2 and 5-LOX in a positive feedback manner. In conclusion, HBx enhances and maintains liver cell proliferation via a positive feedback loop involving COX-2, 5-LOX, released arachidonic acid metabolites, Gi/o proteins and p-ERK1/2.
