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Yi-ling Lin - One of the best experts on this subject based on the ideXlab platform.

  • Human Kinase/Phosphatase-Wide RNAi Screening Identified Checkpoint Kinase 2 as a Cellular Factor Facilitating Japanese Encephalitis Virus Infection.
    Frontiers in cellular and infection microbiology, 2018
    Co-Authors: Yi-lin Chan, Ching-len Liao, Yi-ling Lin
    Abstract:

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes acute encephalitis in humans with high mortality. Not much is known about the interactions between viral and cellular factors that regulate JEV infection. By using a Kinase/phosphatase-wide RNAi screening approach, we identified a cell cycle-regulating molecule, Checkpoint Kinase 2 (CHK2), that plays a role in regulating JEV replication. JEV infection induced G1 arrest and activated CHK2. Inactivation of CHK2 and its upstream ataxia-telangiectasia mutated Kinase in JEV-infected cells by using inhibitors reduced virus replication. Likewise, JEV replication was significantly decreased by knockdown of CHK2 expression with shRNA-producing lentiviral transduction. We identified CHK2 as a cellular factor participating in JEV replication, for a new strategy in addressing JEV infection.

  • human Kinase phosphatase wide rnai screening identified Checkpoint Kinase 2 as a cellular factor facilitating japanese encephalitis virus infection
    Frontiers in Cellular and Infection Microbiology, 2018
    Co-Authors: Yi-lin Chan, Ching-len Liao, Yi-ling Lin
    Abstract:

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes acute encephalitis in humans with high mortality. Not much is known about the interactions between viral and cellular factors that regulate JEV infection. By using a Kinase/phosphatase-wide RNAi screening approach, we identified a cell cycle-regulating molecule, Checkpoint Kinase 2 (CHK2), that plays a role in regulating JEV replication. JEV infection induced G1 arrest and activated CHK2. Inactivation of CHK2 and its upstream ataxia-telangiectasia mutated Kinase in JEV-infected cells by using inhibitors reduced virus replication. Likewise, JEV replication was significantly decreased by knockdown of CHK2 expression with shRNA-producing lentiviral transduction. We identified CHK2 as a cellular factor participating in JEV replication, for a new strategy in addressing JEV infection.

Yi-lin Chan - One of the best experts on this subject based on the ideXlab platform.

  • Human Kinase/Phosphatase-Wide RNAi Screening Identified Checkpoint Kinase 2 as a Cellular Factor Facilitating Japanese Encephalitis Virus Infection.
    Frontiers in cellular and infection microbiology, 2018
    Co-Authors: Yi-lin Chan, Ching-len Liao, Yi-ling Lin
    Abstract:

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes acute encephalitis in humans with high mortality. Not much is known about the interactions between viral and cellular factors that regulate JEV infection. By using a Kinase/phosphatase-wide RNAi screening approach, we identified a cell cycle-regulating molecule, Checkpoint Kinase 2 (CHK2), that plays a role in regulating JEV replication. JEV infection induced G1 arrest and activated CHK2. Inactivation of CHK2 and its upstream ataxia-telangiectasia mutated Kinase in JEV-infected cells by using inhibitors reduced virus replication. Likewise, JEV replication was significantly decreased by knockdown of CHK2 expression with shRNA-producing lentiviral transduction. We identified CHK2 as a cellular factor participating in JEV replication, for a new strategy in addressing JEV infection.

  • human Kinase phosphatase wide rnai screening identified Checkpoint Kinase 2 as a cellular factor facilitating japanese encephalitis virus infection
    Frontiers in Cellular and Infection Microbiology, 2018
    Co-Authors: Yi-lin Chan, Ching-len Liao, Yi-ling Lin
    Abstract:

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes acute encephalitis in humans with high mortality. Not much is known about the interactions between viral and cellular factors that regulate JEV infection. By using a Kinase/phosphatase-wide RNAi screening approach, we identified a cell cycle-regulating molecule, Checkpoint Kinase 2 (CHK2), that plays a role in regulating JEV replication. JEV infection induced G1 arrest and activated CHK2. Inactivation of CHK2 and its upstream ataxia-telangiectasia mutated Kinase in JEV-infected cells by using inhibitors reduced virus replication. Likewise, JEV replication was significantly decreased by knockdown of CHK2 expression with shRNA-producing lentiviral transduction. We identified CHK2 as a cellular factor participating in JEV replication, for a new strategy in addressing JEV infection.

Carol Prives - One of the best experts on this subject based on the ideXlab platform.

  • Stability of Checkpoint Kinase 2 Is Regulated via Phosphorylation at Serine 456
    The Journal of biological chemistry, 2007
    Co-Authors: Elizabeth M. Kass, Jinwoo Ahn, Tomoaki Tanaka, William A. Freed-pastor, Susan Keezer, Carol Prives
    Abstract:

    Checkpoint Kinase 2 (Chk2), a DNA damage-activated protein Kinase, is phosphorylated at Thr-68 by ataxia telangiectasia mutated leading to its activation by phosphorylation at several additional sites. Using mass spectrometry we identified a new Chk2 phosphorylation site at Ser-456. We show that phosphorylation of Ser-456 plays a role in the regulation of Chk2 stability particularly after DNA damage. Mutation of Ser-456 to alanine results in hyperubiquitination of Chk2 and dramatically reduced Chk2 stability. Furthermore, cells expressing S456A Chk2 show a reduction in the apoptotic response to DNA damage. These findings suggest a mechanism for stabilization of Chk2 in response to DNA damage via phosphorylation at Ser-456 and proteasome-dependent turnover of Chk2 protein via dephosphorylation of the same residue.

  • The Chk2 protein Kinase
    DNA Repair, 2004
    Co-Authors: Jinwoo Ahn, Marshall Urist, Carol Prives
    Abstract:

    Checkpoint Kinase 2 (Chk2) is a multifunctional enzyme whose functions are central to the induction of cell cycle arrest and apoptosis by DNA damage. Insight into Chk2 has derived from multiple approaches. Biochemical studies have addressed Chk2 structure, domain organization and regulation by phosphorylation. Extensive work has been done to identify factors that recognize and respond to DNA damage in order to activate Chk2. In turn a number of substrates and targets of Chk2 have been identified that play roles in the Checkpoint response. The roles and regulation of Chk2 have been elucidated by studies in model genetic systems extending from worms and flies to mice and humans. The relationship of Chk2 to human cancer studies is developing rapidly with increasing evidence that Chk2 plays a role in tumor suppression.

  • Questioning the role of Checkpoint Kinase 2 in the p53 DNA damage response.
    The Journal of biological chemistry, 2003
    Co-Authors: Jinwoo Ahn, Marshall Urist, Carol Prives
    Abstract:

    Abstract Cdc25C and p53 have been reported to be physiological targets of Checkpoint Kinase 2 (Chk2). Surprisingly, although Chk2 purified from DNA damage sustaining cells has dramatically increased ability to phosphorylate Cdc25C when compared with untreated cells, its ability to phosphorylate p53 is weak before treatment, and there is no increase in its activity toward p53 after DNA damage by γ irradiation or the radiomimetic agent neocarzinostatin. Furthermore, introduction of Chk2 short interfering RNA into three different human tumor cell lines leads to marked reduction of Chk2 protein, but p53 is still stabilized and active after DNA damage. The results with Chk1 short interfering RNA indicate as well that Chk1 does not play a role in human p53 stabilization after DNA damage. Thus, Chk1 and Chk2 are unlikely to be regulators of p53 in at least some human tumor cells. We discuss our results in the context of previous findings demonstrating a requirement for Chk2 in p53 stabilization and activity.

  • Checkpoint Kinase 2 chk2 monomers or dimers phosphorylate cdc25c after dna damage regardless of threonine 68 phosphorylation
    Journal of Biological Chemistry, 2002
    Co-Authors: Jinwoo Ahn, Carol Prives
    Abstract:

    We have purified and characterized human Chk2 both from baculovirus-infected insect cells and from either untreated or DNA damage-stressed human HCT116 cells. Chk2 from unstressed human cells is largely monomeric and inactive in phosphorylating its substrate, Cdc25C. It is also unphosphorylated at Thr-68, a site that is the target of the ataxia telangiectasia-mutated protein Kinase. After treatment of HCT116 cells with a radiomimetic compound neocarzinostatin, active Chk2 exists as stable Thr-68-phosphorylated dimers as well as interconvertable Thr-68-unphosphorylated monomers and dimers. Interestingly, Chk2 from insect cells behaves by all criteria tested like active Chk2 from neocarzinostatin-treated HCT116 cells. Based on Stokes radius and sedimentation coefficient values, Chk2 monomers and dimers have asymmetric rather than globular shapes. Both Thr-68-phosphorylated and Thr-68-unphosphorylated forms of active Chk2 are capable of phosphorylating Cdc25C. Thus, although phosphorylation of Thr-68 may be required for initial oligomerization and activation of Chk2, it is not needed for maintenance of dimerization or Kinase activity.

Ching-len Liao - One of the best experts on this subject based on the ideXlab platform.

  • Human Kinase/Phosphatase-Wide RNAi Screening Identified Checkpoint Kinase 2 as a Cellular Factor Facilitating Japanese Encephalitis Virus Infection.
    Frontiers in cellular and infection microbiology, 2018
    Co-Authors: Yi-lin Chan, Ching-len Liao, Yi-ling Lin
    Abstract:

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes acute encephalitis in humans with high mortality. Not much is known about the interactions between viral and cellular factors that regulate JEV infection. By using a Kinase/phosphatase-wide RNAi screening approach, we identified a cell cycle-regulating molecule, Checkpoint Kinase 2 (CHK2), that plays a role in regulating JEV replication. JEV infection induced G1 arrest and activated CHK2. Inactivation of CHK2 and its upstream ataxia-telangiectasia mutated Kinase in JEV-infected cells by using inhibitors reduced virus replication. Likewise, JEV replication was significantly decreased by knockdown of CHK2 expression with shRNA-producing lentiviral transduction. We identified CHK2 as a cellular factor participating in JEV replication, for a new strategy in addressing JEV infection.

  • human Kinase phosphatase wide rnai screening identified Checkpoint Kinase 2 as a cellular factor facilitating japanese encephalitis virus infection
    Frontiers in Cellular and Infection Microbiology, 2018
    Co-Authors: Yi-lin Chan, Ching-len Liao, Yi-ling Lin
    Abstract:

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes acute encephalitis in humans with high mortality. Not much is known about the interactions between viral and cellular factors that regulate JEV infection. By using a Kinase/phosphatase-wide RNAi screening approach, we identified a cell cycle-regulating molecule, Checkpoint Kinase 2 (CHK2), that plays a role in regulating JEV replication. JEV infection induced G1 arrest and activated CHK2. Inactivation of CHK2 and its upstream ataxia-telangiectasia mutated Kinase in JEV-infected cells by using inhibitors reduced virus replication. Likewise, JEV replication was significantly decreased by knockdown of CHK2 expression with shRNA-producing lentiviral transduction. We identified CHK2 as a cellular factor participating in JEV replication, for a new strategy in addressing JEV infection.

Yi Charlie Chen - One of the best experts on this subject based on the ideXlab platform.

  • theaflavin 3 3 digallate suppresses human ovarian carcinoma ovcar 3 cells by regulating the Checkpoint Kinase 2 and p27 kip1 pathways
    Molecules, 2019
    Co-Authors: Ying Gao, Junfeng Yin, Yi Charlie Chen
    Abstract:

    Theaflavin-3,3'-digallate (TF3) is a unique polyphenol in black tea. Epidemiological studies have proved that black tea consumption decreases the incidence rate of ovarian cancer. Our former research demonstrated that TF3 inhibited human ovarian cancer cells. Nevertheless, the roles of Checkpoint Kinase 2 (Chk2) and p27 kip1 (p27) in TF3-mediated inhibition of human ovarian cancer cells have not yet been investigated. In the current study, TF3 enhanced the phosphorylation of Chk2 to modulate the ratio of pro/anti-apoptotic Bcl-2 family proteins to initiate intrinsic apoptosis in a p53-independent manner and increased the expression of death receptors to activate extrinsic apoptosis in OVCAR-3 human ovarian carcinoma cells. In addition, TF3 up-regulated the expression of p27 to induce G0/G1 cell cycle arrest in OVCAR-3 cells. Our study indicated that Chk2 and p27 were vital anticancer targets of TF3 and provided more evidence that TF3 might be a potent agent to be applied as adjuvant treatment for ovarian cancer.

  • Theaflavin-3,3′-Digallate Suppresses Human Ovarian Carcinoma OVCAR-3 Cells by Regulating the Checkpoint Kinase 2 and p27 kip1 Pathways
    MDPI AG, 2019
    Co-Authors: Ying Gao, Junfeng Yin, Yi Charlie Chen
    Abstract:

    Theaflavin-3,3242;-digallate (TF3) is a unique polyphenol in black tea. Epidemiological studies have proved that black tea consumption decreases the incidence rate of ovarian cancer. Our former research demonstrated that TF3 inhibited human ovarian cancer cells. Nevertheless, the roles of Checkpoint Kinase 2 (Chk2) and p27 kip1 (p27) in TF3-mediated inhibition of human ovarian cancer cells have not yet been investigated. In the current study, TF3 enhanced the phosphorylation of Chk2 to modulate the ratio of pro/anti-apoptotic Bcl-2 family proteins to initiate intrinsic apoptosis in a p53-independent manner and increased the expression of death receptors to activate extrinsic apoptosis in OVCAR-3 human ovarian carcinoma cells. In addition, TF3 up-regulated the expression of p27 to induce G0/G1 cell cycle arrest in OVCAR-3 cells. Our study indicated that Chk2 and p27 were vital anticancer targets of TF3 and provided more evidence that TF3 might be a potent agent to be applied as adjuvant treatment for ovarian cancer