Transforming growth factor β （TGFβ） controls cellular behavior in embryonic and adult tissues. TGFβ binding to serine/threonine kinase receptors on the plasma membrane activates Smad molecules and additional sign...Transforming growth factor β （TGFβ） controls cellular behavior in embryonic and adult tissues. TGFβ binding to serine/threonine kinase receptors on the plasma membrane activates Smad molecules and additional signaling proteins that together regulate gene expression. In this review, mechanisms and models that aim at explaining the coordination between several components of the signaling network downstream of TGFβ are presented. We discuss how the activity and duration of TGFβ receptor/Smad signaling can be regulated by post-translational modifications that affect the stability of key proteins in the pathway. We highlight finks between these mechanisms and human diseases, such as tissue fibrosis and cancer.展开更多
Post-translational modifications of proteins by small ubiquitin-like modifiers （SUMOs） play crucial roles in plant growth and development, and in stress responses. The MMS21 is a newly-identified Arabidopsis thalian...Post-translational modifications of proteins by small ubiquitin-like modifiers （SUMOs） play crucial roles in plant growth and development, and in stress responses. The MMS21 is a newly-identified Arabidopsis thaliana L. SUMO E3 ligase gene aside from the SIZ1, and its function requires further elucidation. Here, we show that MMS21 deficient plants display improved drought tolerance, and constitutive expression of MMS21 reduces drought tolerance. The expression of MMS21 was reduced by abscisic acid （ABA）, polyethylene glycol （PEG） or drought stress. Under drought conditions, mms21 mutants showed the highest survival rate and the slowest water loss, and accumulated a higher level of free proline compared to wild-type （WT） and MMS21 over-expression plants. Stomatal aperture, seed germination and cotyledon greening analysis indicated that mms21 was hypersensitive to ABA. Molecular genetic analysis revealed that MMS21 deficiency led to elevated expression of a series of ABA-mediated stress-responsive genes, including COR15A, RD22, and P5CS1 The ABA and drought-induced stress-responsive genes, including RAB18, RD29A and RD29B, were inhibited by constitutive expression of MMS21. Moreover, ABA-induced accumulation of SUMO-protein conjugates was blocked in the mms21 mutant. We thus conclude that MMS21 plays a role in the drought stress response, likely through regulation of gene expression in an ABA-dependent pathway.展开更多
Plant immune responses are tightly regulated to ensure their appropriate deployment. Overexpression of TOPLESS-RELATED 1 (TPR1), a SUPPRESSOR OF npr1-1, CONSTITUTIVE 1 (SNC1)-interacting protein, results in autoimmuni...Plant immune responses are tightly regulated to ensure their appropriate deployment. Overexpression of TOPLESS-RELATED 1 (TPR1), a SUPPRESSOR OF npr1-1, CONSTITUTIVE 1 (SNC1)-interacting protein, results in autoimmunity that reduces plant growth and development. However, how TPR1 activity is regulated remains unknown. Loss of function of SIZ1, a (SUMO) E3 ligase, induces an autoimmune response, partially due to elevated SNC1 levels. Here we show that SNC1 expression is upregulated in Arabidopsis thaliana siz1-2 due to positive-feedback regulation by salicylic acid. SIZ1 physically interacts with TPR1 and facilitates its SUMO modification. The K282 and K721 residues in TPR1 serve as critical SUMO attachment sites. Simultaneous introduction of K282R and K721R substitutions in TPR1 blocked its SUMOylation, enhaneed its transcriptional co-repressor activity, and increased its association with HISTONE DEACETYLASE 19 (HDA19), suggesting that SUMOylation of TPR1 represses its transcriptional co-repressor activity and inhibits its interaction with HDA19. In agreement with this finding, the simultaneous introduction of K282R and K721R substitutions enhanced TPR1 mediated immunity, and the tpr1 mutation partially suppressed autoimmunity in siz1-2. These results demonstrate that SIZ1-mediated SUMOylation of TPR1 represses plant immunity, which at least partly contributes to the suppression of autoimmunity under nonpathogenic conditions to ensure proper plant development.展开更多
深度强化学习(DRL)广泛应用于具有高度不确定性的城市交通信号控制问题中,但现有的DRL交通信号控制方法中,仅仅使用传统的深度神经网络,复杂交通场景下其感知能力有限。此外,状态作为强化学习的三要素之一,现有方法中的交通状态也需要...深度强化学习(DRL)广泛应用于具有高度不确定性的城市交通信号控制问题中,但现有的DRL交通信号控制方法中,仅仅使用传统的深度神经网络,复杂交通场景下其感知能力有限。此外,状态作为强化学习的三要素之一,现有方法中的交通状态也需要人工精心的设计。因此,提出了一种基于注意力机制(attention mecha-nism)的DRL交通信号控制算法。通过引入注意力机制,使得神经网络自动地关注重要的状态分量以增强网络的感知能力,提升了信号控制效果,并减少了状态向量设计的难度。在SUMO(simulation of urban mobility)仿真平台上的实验结果表明,在单交叉口、多交叉口中,在低、高交通流量条件下,仅仅使用简单的交通状态,与三种基准信号控制算法相比,所提算法在平均等待时间、行驶时间等指标上都具有最好的性能。展开更多
SUMOylation is an impo^ant post-translational modification process that regulates different cellular functions in eukaryotes. SIZ/PIAS-type SAP and Mizl （SIZ0 proteins exhibit SUMO E3 ligase activity, which modulates...SUMOylation is an impo^ant post-translational modification process that regulates different cellular functions in eukaryotes. SIZ/PIAS-type SAP and Mizl （SIZ0 proteins exhibit SUMO E3 ligase activity, which modulates SUMOylation. However, SIZI in tomato has been rarely investigated. In this study, a tomato SIZI gene （SISIZI） was isolated and its molecular characteristics and role in tolerance to drought stress are described. SISIZI was upregulated by cold, sodium chloride （NaCI）, polyethylene glycol （PEG）, hydrogen peroxide （H20~） and abscisic acid （ABA）, and the corresponding proteins were localized in the nucleus. The expression of SISIZI in Arabidopsis thaliana （Arabidopsis） sizl-2 mutants partially complemented the phenotypes of dwarf, cold sensitivity and ABA hypersensitivity. SISIZI also exhibited the activity of SUMO E3 ligase to promote the accumulation of SUMO conjugates. Under drought stress, the ectopic expression of SISIZl in transgenic tobacco lines enhanced seed germination and reduced the accumulation of reactive oxygen species..SISIZl overexpression conferred the plants with improved growth, high free proline content, minimal malondialdehyde accumulation and increased accumulation of SUMO conjugates. SISIZ1 is a functional homolog of Arabidopsis SIZ1 with SUMO E3 ligase activity. Therefore, overexpression of SISIZ1 enhanced the tolerance of transgenic tobacco to drought stress.展开更多
We recently report that the expression of polycomb chromobox 4(Cbx4)is significantly correlated with the overall survival of a great cohort of hepatocellular carcinoma(HCC)patients and it enhances hypoxia-induced vasc...We recently report that the expression of polycomb chromobox 4(Cbx4)is significantly correlated with the overall survival of a great cohort of hepatocellular carcinoma(HCC)patients and it enhances hypoxia-induced vascular endothelial growth factor(VEGF)expression and angiogenesis in HCC cells through enhancing sumoylation of hypoxia inducible factor-1alpha(HIF-1α).Here we continue to investigate the potential effects of Cbx4 on the migration and metastasis of the metastatic HCC cell line MHCC97L.Our results show that Cbx4 overexpression in the cell line increases the in vitro vessel formation of vascular endothelial cells in its SUMO interaction motifs-dependent manner,and promotes the in vitro migration of the cancer cell,which can be effectively abrogated by anti-VEGF antibody.Although Cbx4 expression does not impact the in vitro growth of MHCC97L cells,it still promotes the progression and metastasis of orthotopically transplanted tumors in nude mice.These results further support the role of Cbx4 as a SUMO E3 ligase in the progression and metastasis of HCC.展开更多
文摘Transforming growth factor β （TGFβ） controls cellular behavior in embryonic and adult tissues. TGFβ binding to serine/threonine kinase receptors on the plasma membrane activates Smad molecules and additional signaling proteins that together regulate gene expression. In this review, mechanisms and models that aim at explaining the coordination between several components of the signaling network downstream of TGFβ are presented. We discuss how the activity and duration of TGFβ receptor/Smad signaling can be regulated by post-translational modifications that affect the stability of key proteins in the pathway. We highlight finks between these mechanisms and human diseases, such as tissue fibrosis and cancer.
基金supported by the National Natural ScienceFoundation of China (30900789, 31170269)the Ministry of Agriculture (National Key Program for Transgenic breeding 2009ZX08009-006B)the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2010
文摘Post-translational modifications of proteins by small ubiquitin-like modifiers （SUMOs） play crucial roles in plant growth and development, and in stress responses. The MMS21 is a newly-identified Arabidopsis thaliana L. SUMO E3 ligase gene aside from the SIZ1, and its function requires further elucidation. Here, we show that MMS21 deficient plants display improved drought tolerance, and constitutive expression of MMS21 reduces drought tolerance. The expression of MMS21 was reduced by abscisic acid （ABA）, polyethylene glycol （PEG） or drought stress. Under drought conditions, mms21 mutants showed the highest survival rate and the slowest water loss, and accumulated a higher level of free proline compared to wild-type （WT） and MMS21 over-expression plants. Stomatal aperture, seed germination and cotyledon greening analysis indicated that mms21 was hypersensitive to ABA. Molecular genetic analysis revealed that MMS21 deficiency led to elevated expression of a series of ABA-mediated stress-responsive genes, including COR15A, RD22, and P5CS1 The ABA and drought-induced stress-responsive genes, including RAB18, RD29A and RD29B, were inhibited by constitutive expression of MMS21. Moreover, ABA-induced accumulation of SUMO-protein conjugates was blocked in the mms21 mutant. We thus conclude that MMS21 plays a role in the drought stress response, likely through regulation of gene expression in an ABA-dependent pathway.
基金the Chinese Academy of Sciences (XDA08010105)the National Natural Science Foundation of China (grant no. 31670186 and 31471363).
文摘Plant immune responses are tightly regulated to ensure their appropriate deployment. Overexpression of TOPLESS-RELATED 1 (TPR1), a SUPPRESSOR OF npr1-1, CONSTITUTIVE 1 (SNC1)-interacting protein, results in autoimmunity that reduces plant growth and development. However, how TPR1 activity is regulated remains unknown. Loss of function of SIZ1, a (SUMO) E3 ligase, induces an autoimmune response, partially due to elevated SNC1 levels. Here we show that SNC1 expression is upregulated in Arabidopsis thaliana siz1-2 due to positive-feedback regulation by salicylic acid. SIZ1 physically interacts with TPR1 and facilitates its SUMO modification. The K282 and K721 residues in TPR1 serve as critical SUMO attachment sites. Simultaneous introduction of K282R and K721R substitutions in TPR1 blocked its SUMOylation, enhaneed its transcriptional co-repressor activity, and increased its association with HISTONE DEACETYLASE 19 (HDA19), suggesting that SUMOylation of TPR1 represses its transcriptional co-repressor activity and inhibits its interaction with HDA19. In agreement with this finding, the simultaneous introduction of K282R and K721R substitutions enhanced TPR1 mediated immunity, and the tpr1 mutation partially suppressed autoimmunity in siz1-2. These results demonstrate that SIZ1-mediated SUMOylation of TPR1 represses plant immunity, which at least partly contributes to the suppression of autoimmunity under nonpathogenic conditions to ensure proper plant development.
文摘深度强化学习(DRL)广泛应用于具有高度不确定性的城市交通信号控制问题中,但现有的DRL交通信号控制方法中,仅仅使用传统的深度神经网络,复杂交通场景下其感知能力有限。此外,状态作为强化学习的三要素之一,现有方法中的交通状态也需要人工精心的设计。因此,提出了一种基于注意力机制(attention mecha-nism)的DRL交通信号控制算法。通过引入注意力机制,使得神经网络自动地关注重要的状态分量以增强网络的感知能力,提升了信号控制效果,并减少了状态向量设计的难度。在SUMO(simulation of urban mobility)仿真平台上的实验结果表明,在单交叉口、多交叉口中,在低、高交通流量条件下,仅仅使用简单的交通状态,与三种基准信号控制算法相比,所提算法在平均等待时间、行驶时间等指标上都具有最好的性能。
基金supported by the State Key Basic Research and Development Plan of China(2015CB150105)the Natural Science Foundation of China(31171474,31371553)
文摘SUMOylation is an impo^ant post-translational modification process that regulates different cellular functions in eukaryotes. SIZ/PIAS-type SAP and Mizl （SIZ0 proteins exhibit SUMO E3 ligase activity, which modulates SUMOylation. However, SIZI in tomato has been rarely investigated. In this study, a tomato SIZI gene （SISIZI） was isolated and its molecular characteristics and role in tolerance to drought stress are described. SISIZI was upregulated by cold, sodium chloride （NaCI）, polyethylene glycol （PEG）, hydrogen peroxide （H20~） and abscisic acid （ABA）, and the corresponding proteins were localized in the nucleus. The expression of SISIZI in Arabidopsis thaliana （Arabidopsis） sizl-2 mutants partially complemented the phenotypes of dwarf, cold sensitivity and ABA hypersensitivity. SISIZI also exhibited the activity of SUMO E3 ligase to promote the accumulation of SUMO conjugates. Under drought stress, the ectopic expression of SISIZl in transgenic tobacco lines enhanced seed germination and reduced the accumulation of reactive oxygen species..SISIZl overexpression conferred the plants with improved growth, high free proline content, minimal malondialdehyde accumulation and increased accumulation of SUMO conjugates. SISIZ1 is a functional homolog of Arabidopsis SIZ1 with SUMO E3 ligase activity. Therefore, overexpression of SISIZ1 enhanced the tolerance of transgenic tobacco to drought stress.
基金supported by the National Natural Science Foundation of China (91213304,31101044)Shanghai Science and Technology Committee (11JC1406800)Shanghai Committee of Education
文摘We recently report that the expression of polycomb chromobox 4(Cbx4)is significantly correlated with the overall survival of a great cohort of hepatocellular carcinoma(HCC)patients and it enhances hypoxia-induced vascular endothelial growth factor(VEGF)expression and angiogenesis in HCC cells through enhancing sumoylation of hypoxia inducible factor-1alpha(HIF-1α).Here we continue to investigate the potential effects of Cbx4 on the migration and metastasis of the metastatic HCC cell line MHCC97L.Our results show that Cbx4 overexpression in the cell line increases the in vitro vessel formation of vascular endothelial cells in its SUMO interaction motifs-dependent manner,and promotes the in vitro migration of the cancer cell,which can be effectively abrogated by anti-VEGF antibody.Although Cbx4 expression does not impact the in vitro growth of MHCC97L cells,it still promotes the progression and metastasis of orthotopically transplanted tumors in nude mice.These results further support the role of Cbx4 as a SUMO E3 ligase in the progression and metastasis of HCC.
