The Experts below are selected from a list of 1557 Experts worldwide ranked by ideXlab platform

Yong-li Bao - One of the best experts on this subject based on the ideXlab platform.

  • The Threonine Protease Activity of Testes-Specific Protease 50 (TSP50) Is Essential for Its Function in Cell Proliferation
    2013
    Co-Authors: Yong-li Bao, Zhen-bo Song, Lu-guo Sun, Yu Zhang, Cong Fan, Xin Huang
    Abstract:

    Background: Testes-specific Protease 50 (TSP50), a newly discovered Threonine enzyme, has similar amino acid sequences and enzymatic structures to those of many serine Proteases. It may be an oncogene. TSP50 is up-regulated in breast cancer epithelial cells, and ectopic expression of TSP50 in TSP50-deficient Chinese hamster ovary (CHO) cells has been found to promote cell proliferation. However, the mechanisms by which TSP50 exerts its growth-promoting effects are not yet fully understood. Methodology/Principal Findings: To delineate whether the Threonine Protease activity of TSP50 is essential to its function in cell proliferation, we constructed and characterized a mutant TSP50, called TSP50 T310A, which was identified as a Protease-dead mutant of TSP50. By a series of proliferation analyses, colony formation assays and apoptosis analyses, we showed that T310A mutation significantly depresses TSP50-induced cell proliferation in vitro. Next, the CHO stable cell line expressing either wild-type or T310A mutant TSP50 was injected subcutaneously into nude mice. We found that the T310A mutation could abolish the tumorigenicity of TSP50 in vivo. A mechanism investigation revealed that the T310A mutation prevented interaction between TSP50 and the NF-kBIkBa complex, which is necessary for TSP50 to perform its function in cell proliferation. Conclusion: Our data highlight the importance of Threonine 310, the most critical Protease catalytic site in TSP50, to TSP50induce

  • knockdown of tsp50 inhibits cell proliferation and induces apoptosis in p19 cells
    Iubmb Life, 2010
    Co-Authors: Yong-li Bao, Yu Zhang, Yanxin Huang, Ying Sun, Lihua Zheng
    Abstract:

    Earlier studies identified testes-specific Protease 50 (TSP50), which encodes a Threonine Protease, and showed that it was abnormally reactivated in many breast cancer biopsies. Further, it was shown to be negatively regulated by the p53 gene. However, little is known about the biological function of TSP50. In this study, we applied RNA interference to knockdown TSP50 gene expression in P19 murine embryonal carcinoma stem cells and tested whether this modulated the cell phenotype. The results showed that downregulation of TSP50 expression not only reduced cell proliferation, colony formation, and migration but also induced cell apoptosis. Further investigation revealed that knockdown of TSP50 resulted in greater sensitivity to doxorubicin-induced apoptosis and that activation of caspase-3 was involved in this process.

Lihua Zheng - One of the best experts on this subject based on the ideXlab platform.

  • knockdown of tsp50 inhibits cell proliferation and induces apoptosis in p19 cells
    Iubmb Life, 2010
    Co-Authors: Yong-li Bao, Yu Zhang, Yanxin Huang, Ying Sun, Lihua Zheng
    Abstract:

    Earlier studies identified testes-specific Protease 50 (TSP50), which encodes a Threonine Protease, and showed that it was abnormally reactivated in many breast cancer biopsies. Further, it was shown to be negatively regulated by the p53 gene. However, little is known about the biological function of TSP50. In this study, we applied RNA interference to knockdown TSP50 gene expression in P19 murine embryonal carcinoma stem cells and tested whether this modulated the cell phenotype. The results showed that downregulation of TSP50 expression not only reduced cell proliferation, colony formation, and migration but also induced cell apoptosis. Further investigation revealed that knockdown of TSP50 resulted in greater sensitivity to doxorubicin-induced apoptosis and that activation of caspase-3 was involved in this process.

Yu Zhang - One of the best experts on this subject based on the ideXlab platform.

  • The Threonine Protease Activity of Testes-Specific Protease 50 (TSP50) Is Essential for Its Function in Cell Proliferation
    2013
    Co-Authors: Yong-li Bao, Zhen-bo Song, Lu-guo Sun, Yu Zhang, Cong Fan, Xin Huang
    Abstract:

    Background: Testes-specific Protease 50 (TSP50), a newly discovered Threonine enzyme, has similar amino acid sequences and enzymatic structures to those of many serine Proteases. It may be an oncogene. TSP50 is up-regulated in breast cancer epithelial cells, and ectopic expression of TSP50 in TSP50-deficient Chinese hamster ovary (CHO) cells has been found to promote cell proliferation. However, the mechanisms by which TSP50 exerts its growth-promoting effects are not yet fully understood. Methodology/Principal Findings: To delineate whether the Threonine Protease activity of TSP50 is essential to its function in cell proliferation, we constructed and characterized a mutant TSP50, called TSP50 T310A, which was identified as a Protease-dead mutant of TSP50. By a series of proliferation analyses, colony formation assays and apoptosis analyses, we showed that T310A mutation significantly depresses TSP50-induced cell proliferation in vitro. Next, the CHO stable cell line expressing either wild-type or T310A mutant TSP50 was injected subcutaneously into nude mice. We found that the T310A mutation could abolish the tumorigenicity of TSP50 in vivo. A mechanism investigation revealed that the T310A mutation prevented interaction between TSP50 and the NF-kBIkBa complex, which is necessary for TSP50 to perform its function in cell proliferation. Conclusion: Our data highlight the importance of Threonine 310, the most critical Protease catalytic site in TSP50, to TSP50induce

  • knockdown of tsp50 inhibits cell proliferation and induces apoptosis in p19 cells
    Iubmb Life, 2010
    Co-Authors: Yong-li Bao, Yu Zhang, Yanxin Huang, Ying Sun, Lihua Zheng
    Abstract:

    Earlier studies identified testes-specific Protease 50 (TSP50), which encodes a Threonine Protease, and showed that it was abnormally reactivated in many breast cancer biopsies. Further, it was shown to be negatively regulated by the p53 gene. However, little is known about the biological function of TSP50. In this study, we applied RNA interference to knockdown TSP50 gene expression in P19 murine embryonal carcinoma stem cells and tested whether this modulated the cell phenotype. The results showed that downregulation of TSP50 expression not only reduced cell proliferation, colony formation, and migration but also induced cell apoptosis. Further investigation revealed that knockdown of TSP50 resulted in greater sensitivity to doxorubicin-induced apoptosis and that activation of caspase-3 was involved in this process.

Hsieh, James J - One of the best experts on this subject based on the ideXlab platform.

  • Taspase1 orchestrates fetal liver hematopoietic stem cell and vertebrae fates by cleaving TFIIA
    Digital Commons@Becker, 2021
    Co-Authors: Niizuma Hidetaka, Searleman, Adam C, Takeda Shugaku, Armstrong, Scott A, Park, Christopher Y, Cheng, Emily H, Hsieh, James J
    Abstract:

    Taspase1, a highly conserved Threonine Protease encoded by TASP1, cleaves nuclear histone-modifying factors and basal transcription regulators to orchestrate diverse transcription programs. Hereditary loss-of-function mutation of TASP1 has recently been reported in humans as resulting in an anomaly complex syndrome, which manifests with hematological, facial, and skeletal abnormalities. Here, we demonstrate that Taspase1-mediated cleavage of TFIIAα-β, rather than of MLL1 or MLL2, in mouse embryos was required for proper fetal liver hematopoiesis and correct segmental identities of the axial skeleton. Homozygous genetic deletion of Taspase1 disrupted embryonic hematopoietic stem cell self-renewal and quiescence states and axial skeleton fates. Strikingly, mice carrying knockin noncleavable mutations of TFIIAα-β, a well-characterized basal transcription factor, displayed more pronounced fetal liver and axial skeleton defects than those with noncleavable MLL1 and MLL2, 2 trithorax group histone H3 trimethyl transferases. Our study offers molecular insights into a syndrome in humans that results from loss of TASP1 and describes an unexpected role of TFIIAα-β cleavage in embryonic cell fate decisions

James J Hsieh - One of the best experts on this subject based on the ideXlab platform.

  • taspase1 orchestrates fetal liver hematopoietic stem cell and vertebrae fates through cleaving tfiia
    JCI insight, 2021
    Co-Authors: Hidetaka Niizuma, Adam C Searleman, Shugaku Takeda, Scott A Armstrong, Christopher Y Park, Emily H Cheng, James J Hsieh
    Abstract:

    Taspase1, a highly conserved Threonine Protease encoded by TASP1, cleaves nuclear histone modifying factors and basal transcription regulators to orchestrate diverse transcription programs. Hereditary loss-of-function mutation of TASP1 has recently been reported in human resulting in a novel anomaly complex syndrome manifested with hematological, facial, and skeletal abnormalities. Here, we demonstrate that Taspase1-mediated cleavage of TFIIAα-β, rather than of MLL1 or MLL2, in mouse embryos is required for proper fetal liver hematopoiesis and correct segmental identities of the axial skeleton. Homozygous genetic deletion of Taspase1 (Tasp1-/-) disrupted embryonic hematopoietic stem cell self-renewal and quiescence states, and axial skeleton fates. Strikingly, mice carrying knockin non-cleavable mutations of TFIIAα-β (Gtf2a1nc/nc), a well-characterized basal transcription factor, displayed more pronounced fetal liver and axial skeleton defects than those with non-cleavable MLL1 and MLL2 (Mll1nc/nc;2nc/nc), two trithorax group (Trx-G) histone H3 trimethyl transferases. Our study offers molecular insights concerning TASP1-loss human syndrome and discovers unexpected role of TFIIAα-β cleavage in embryonic cell fate decisions.