[目的]研究Netrin1调控ELF3对子宫内膜癌HEC-1B细胞转移活性的影响。[方法]将36份组织样本分为2组:子宫内膜癌组、癌旁组,每组18份。蛋白免疫印迹检测癌组织和癌旁组织中Netrin1与ELF3的表达。将子宫内膜癌HEC-1B细胞设置为3组:siRNA N...[目的]研究Netrin1调控ELF3对子宫内膜癌HEC-1B细胞转移活性的影响。[方法]将36份组织样本分为2组:子宫内膜癌组、癌旁组,每组18份。蛋白免疫印迹检测癌组织和癌旁组织中Netrin1与ELF3的表达。将子宫内膜癌HEC-1B细胞设置为3组:siRNA NC组、siRNA Netrin1组和siRNA ELF3组。MTT实验法检测HEC-1B细胞的增殖能力,细胞划痕实验方法分析HEC-1B细胞的迁移能力,TUNEL实验检测HEC-1B细胞的凋亡率,蛋白免疫印迹方法分析HEC-1B细胞中Netrin1与ELF3蛋白的表达。[结果]与癌旁组织比较,子宫内膜癌组织Netrin1与ELF3的表达上调(0.19±0.06 vs 0.73±0.02,P<0.05;0.23±0.03 vs 0.69±0.08,P<0.05)。与siRNA NC组比较,siRNA Netrin1以及siRNA ELF3组的子宫内膜癌HEC-1B细胞增殖能力下降;siRNA Netrin1以及siRNA ELF3组的HEC-1B细胞迁移能力下降;siRNA Netrin1以及siRNA ELF3组的HEC-1B细胞凋亡率增加(1.15%±0.08%vs 10.31%±0.06%vs 9.96%±0.17%,P<0.05);siRNA Netrin1组的HEC-1B细胞Netrin1、ELF3表达降低(0.78±0.06 vs 0.31±0.07 vs 0.75±0.11,P<0.05;0.73±0.08 vs 0.25±0.03 vs 0.29±0.07,P<0.05);siRNA ELF3组的HEC-1B细胞ELF3表达降低。[结论]子宫内膜癌组织中Netrin1与ELF3的表达水平增加。抑制Netrin1表达后,子宫内膜癌HEC-1B细胞的增殖与迁移能力减弱,凋亡率增加,Netrin1对子宫内膜癌的作用与调控ELF3相关。展开更多
Temperature is a crucial environmental cue that governs plant growth and adaptation in natural habitats.PHYTOCHROME INTERACTING FACTOR 4(PIF4)functions as a central regulator promoting thermomor-phogenesis in Arabidop...Temperature is a crucial environmental cue that governs plant growth and adaptation in natural habitats.PHYTOCHROME INTERACTING FACTOR 4(PIF4)functions as a central regulator promoting thermomor-phogenesis in Arabidopsis.An understanding of its precise regulation is essential for optimal thermomor-phogenic growth.Here,we identified two BBX proteins,BBX24 and BBX25,as novel components of the PIF4-mediated thermosensory pathway that promote growth at elevated temperatures.Single and double mutants of bbx24 and bbx25 exhibit moderate to strong temperature-insensitive hypocotyl and cotyledon growth.Elevated temperatures induce BBX24 and BBX25 mRNA expression and protein accumulation.Ge-netic and biochemical analyses reveal that BBX24 and BBX25 enhance PIF4-mediated thermosensory growth by counteracting ELF3,a key component of the evening complex.Whereas ELF3 represses BBX24 and BBX25 gene expression at low ambient temperatures during the evening,the inhibition of ELF3 activity under elevated temperatures increases BBX24 and BBX25 activity.Moreover,BBX24 and BBX25 suppress ELF3 function through direct physical interaction,likely relieving its repression of PIF4 and enhancing thermomorphogenesis.These findings identify the ELF3–BBX24/BBX25–PIF4 axis as a key regulatory module controlling plant growth and development in response to temperature cues.展开更多
Plants are capable of coordination of their growth and development with ambient temperatures.EARLY FLOWERING3(ELF3), an essential component of the plant circadian clock, is also involved in ambient temperature sensing...Plants are capable of coordination of their growth and development with ambient temperatures.EARLY FLOWERING3(ELF3), an essential component of the plant circadian clock, is also involved in ambient temperature sensing, as well as in inhibiting the expression and protein activity of the thermoresponsive regulator phytochrome interacting factor4(PIF4). The ELF3 activity is subjected to attenuation in response to warm temperature;however,how the protein level of ELF3 is regulated at warm temperature remains less understood. Here, we report that the E3 ligase XB3 ORTHOLOG 5 IN ARABIDOPSIS THALIANA, XBAT35, mediates ELF3 degradation. XBAT35 interacts with ELF3 and ubiquitinates ELF3. Loss-of-function mutation of XBAT35 increases the protein level of ELF3 and confers a short-hypocotyl phenotype under warm temperature conditions. Thus, our findings establish that XBAT35 mediates ELF3 degradation to lift the inhibition of ELF3 on PIF4 for promoting thermoresponsive hypocotyl growth in plants.展开更多
Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity...Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity to understand the comparative biology of all periampullary malignancies. These neoplasms can exhibit intestinal, pancreaticobiliary or mixed features, whereas the subclassification based on morphology and immunohistochemical features failed in demonstrating a robust prognostic reliability. In the last few years, the molecular landscape of this tumor entity has been uncovered, identifying alterations that may serve as prognostic and predictive biomarkers. In this review, the histological and genetic characteristics of ampullary carcinomas are discussed, taking into account the main clinical and therapeutic implications related to this tumor type as well.展开更多
We investigated the diurnal dependence of the hypocotyl-growth responses to shade under sunlight-night cycles in Arabidopsis thaliana. Afternoon shade events promoted hypocotyl growth, while morning shade was ineffect...We investigated the diurnal dependence of the hypocotyl-growth responses to shade under sunlight-night cycles in Arabidopsis thaliana. Afternoon shade events promoted hypocotyl growth, while morning shade was ineffective. The Ihy-D, elf3, lux, pif4 pifS, tocl, and quadruple della mutants retained the response to afternoon shade and the lack of response to morning shade while the Ihyccal mutant responded to both morning and afternoon shade. ThephyB mutant, plants overexpressing the multidrug resistance-like membrane protein ABCB19, and the iaa17/axr3 loss-of-function mutant failed to respond to shade. Transient exposure of sunlight-grown seedlings to synthetic auxin in the afternoon caused a stronger promotion of hypocotyl growth than morning treatments. The promotion of hypocotyl growth by afternoon shade or afternoon auxin required light perceived by phytochrome A or cryptochromes during the previous hours of the photoperiod. Although the ELF4-ELF3-LUX complex, PIF4, PIF5, and DELLA are key players in the generation of diurnal hypocotyl-growth patterns, they exert a minor role in the control of the diurnal pattern of growth responses to shade. We conclude that the strong diurnal dependency of hypocotyl-growth responses to shade relates to the balance between the antagonistic actions of LHY-CCA1 and a light-derived signal.展开更多
Plants have to cope with the surrounding changing environmental stimuli to optimize their physiological and devel-opmental response throughout their entire life cycle.Light and temperature are two critical environment...Plants have to cope with the surrounding changing environmental stimuli to optimize their physiological and devel-opmental response throughout their entire life cycle.Light and temperature are two critical environmental cues that fluctuate greatly during day-night cycles and seasonal changes.These two external signals coordinately control the plant growth and development.Distinct spectrum of light signals are perceived by a group of wavelength-specific photoreceptors in plants.PIFs and COP1-HY5 are two predominant signaling hubs that control the expression of a large number of light-responsive genes and subsequent light-mediated development in plants.In parallel,plants also transmit low or warm temperature signals to these two regulatory modules that precisely modulate the responsive-ness of low or warm temperatures.The core component of circadian clock ELF3 integrates signals from light and warm temperatures to regulate physiological and developmental processes in plants.In this review,we summarize and discuss recent advances and progresses on PIFs-,COP1-HY5-and ELF3-mediated light,low or warm temperature signaling,and highlight emerging insights regarding the interactions between light and low or warm temperature signal transduction pathways in the control of plant growth.展开更多
文摘[目的]研究Netrin1调控ELF3对子宫内膜癌HEC-1B细胞转移活性的影响。[方法]将36份组织样本分为2组:子宫内膜癌组、癌旁组,每组18份。蛋白免疫印迹检测癌组织和癌旁组织中Netrin1与ELF3的表达。将子宫内膜癌HEC-1B细胞设置为3组:siRNA NC组、siRNA Netrin1组和siRNA ELF3组。MTT实验法检测HEC-1B细胞的增殖能力,细胞划痕实验方法分析HEC-1B细胞的迁移能力,TUNEL实验检测HEC-1B细胞的凋亡率,蛋白免疫印迹方法分析HEC-1B细胞中Netrin1与ELF3蛋白的表达。[结果]与癌旁组织比较,子宫内膜癌组织Netrin1与ELF3的表达上调(0.19±0.06 vs 0.73±0.02,P<0.05;0.23±0.03 vs 0.69±0.08,P<0.05)。与siRNA NC组比较,siRNA Netrin1以及siRNA ELF3组的子宫内膜癌HEC-1B细胞增殖能力下降;siRNA Netrin1以及siRNA ELF3组的HEC-1B细胞迁移能力下降;siRNA Netrin1以及siRNA ELF3组的HEC-1B细胞凋亡率增加(1.15%±0.08%vs 10.31%±0.06%vs 9.96%±0.17%,P<0.05);siRNA Netrin1组的HEC-1B细胞Netrin1、ELF3表达降低(0.78±0.06 vs 0.31±0.07 vs 0.75±0.11,P<0.05;0.73±0.08 vs 0.25±0.03 vs 0.29±0.07,P<0.05);siRNA ELF3组的HEC-1B细胞ELF3表达降低。[结论]子宫内膜癌组织中Netrin1与ELF3的表达水平增加。抑制Netrin1表达后,子宫内膜癌HEC-1B细胞的增殖与迁移能力减弱,凋亡率增加,Netrin1对子宫内膜癌的作用与调控ELF3相关。
基金supported by grants from the Department of Biotechnol-ogy(Ramalingaswami Fellowship Grant,BT/RLF/Re-entry/28/2017)Sci-ence and Engineering Research Board(Start-up Research Grant,SRG/2019/000446)+1 种基金Anusandhan National Research Foundation(Core Research Grant,CRG/2023/001553)Intramural grant(IISER Kolkata),Ministry of Education(MoE/STARS-1/416),Government of India.
文摘Temperature is a crucial environmental cue that governs plant growth and adaptation in natural habitats.PHYTOCHROME INTERACTING FACTOR 4(PIF4)functions as a central regulator promoting thermomor-phogenesis in Arabidopsis.An understanding of its precise regulation is essential for optimal thermomor-phogenic growth.Here,we identified two BBX proteins,BBX24 and BBX25,as novel components of the PIF4-mediated thermosensory pathway that promote growth at elevated temperatures.Single and double mutants of bbx24 and bbx25 exhibit moderate to strong temperature-insensitive hypocotyl and cotyledon growth.Elevated temperatures induce BBX24 and BBX25 mRNA expression and protein accumulation.Ge-netic and biochemical analyses reveal that BBX24 and BBX25 enhance PIF4-mediated thermosensory growth by counteracting ELF3,a key component of the evening complex.Whereas ELF3 represses BBX24 and BBX25 gene expression at low ambient temperatures during the evening,the inhibition of ELF3 activity under elevated temperatures increases BBX24 and BBX25 activity.Moreover,BBX24 and BBX25 suppress ELF3 function through direct physical interaction,likely relieving its repression of PIF4 and enhancing thermomorphogenesis.These findings identify the ELF3–BBX24/BBX25–PIF4 axis as a key regulatory module controlling plant growth and development in response to temperature cues.
基金project was financially supported by grants from the National Natural Science Foundation of China(31625004 and 31872653)the Zhejiang Provincial Talent Program(2019R52005)+1 种基金the BBSRC(BB/N018540/1)the 111 Project(B14027)。
文摘Plants are capable of coordination of their growth and development with ambient temperatures.EARLY FLOWERING3(ELF3), an essential component of the plant circadian clock, is also involved in ambient temperature sensing, as well as in inhibiting the expression and protein activity of the thermoresponsive regulator phytochrome interacting factor4(PIF4). The ELF3 activity is subjected to attenuation in response to warm temperature;however,how the protein level of ELF3 is regulated at warm temperature remains less understood. Here, we report that the E3 ligase XB3 ORTHOLOG 5 IN ARABIDOPSIS THALIANA, XBAT35, mediates ELF3 degradation. XBAT35 interacts with ELF3 and ubiquitinates ELF3. Loss-of-function mutation of XBAT35 increases the protein level of ELF3 and confers a short-hypocotyl phenotype under warm temperature conditions. Thus, our findings establish that XBAT35 mediates ELF3 degradation to lift the inhibition of ELF3 on PIF4 for promoting thermoresponsive hypocotyl growth in plants.
基金Supported by the Italian Association for Cancer Research,No.12182
文摘Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity to understand the comparative biology of all periampullary malignancies. These neoplasms can exhibit intestinal, pancreaticobiliary or mixed features, whereas the subclassification based on morphology and immunohistochemical features failed in demonstrating a robust prognostic reliability. In the last few years, the molecular landscape of this tumor entity has been uncovered, identifying alterations that may serve as prognostic and predictive biomarkers. In this review, the histological and genetic characteristics of ampullary carcinomas are discussed, taking into account the main clinical and therapeutic implications related to this tumor type as well.
文摘We investigated the diurnal dependence of the hypocotyl-growth responses to shade under sunlight-night cycles in Arabidopsis thaliana. Afternoon shade events promoted hypocotyl growth, while morning shade was ineffective. The Ihy-D, elf3, lux, pif4 pifS, tocl, and quadruple della mutants retained the response to afternoon shade and the lack of response to morning shade while the Ihyccal mutant responded to both morning and afternoon shade. ThephyB mutant, plants overexpressing the multidrug resistance-like membrane protein ABCB19, and the iaa17/axr3 loss-of-function mutant failed to respond to shade. Transient exposure of sunlight-grown seedlings to synthetic auxin in the afternoon caused a stronger promotion of hypocotyl growth than morning treatments. The promotion of hypocotyl growth by afternoon shade or afternoon auxin required light perceived by phytochrome A or cryptochromes during the previous hours of the photoperiod. Although the ELF4-ELF3-LUX complex, PIF4, PIF5, and DELLA are key players in the generation of diurnal hypocotyl-growth patterns, they exert a minor role in the control of the diurnal pattern of growth responses to shade. We conclude that the strong diurnal dependency of hypocotyl-growth responses to shade relates to the balance between the antagonistic actions of LHY-CCA1 and a light-derived signal.
基金supported by the Fundamental Research Funds for the Central Universities(KJJQ2022002)the Natural Science Foundation of Jiangsu for Distinguished Young Scholars(BK20211525)+1 种基金the National Natural Science Foundation of China(31970258)the Jiangsu“Innovative and Entrepreneurial Talent”program(to D.X.),the Jiangsu Collaborative Innovation Center for Modern Crop Production(to D.X.)and the Nanjing Agricultural University(start-up funding to D.X.).
文摘Plants have to cope with the surrounding changing environmental stimuli to optimize their physiological and devel-opmental response throughout their entire life cycle.Light and temperature are two critical environmental cues that fluctuate greatly during day-night cycles and seasonal changes.These two external signals coordinately control the plant growth and development.Distinct spectrum of light signals are perceived by a group of wavelength-specific photoreceptors in plants.PIFs and COP1-HY5 are two predominant signaling hubs that control the expression of a large number of light-responsive genes and subsequent light-mediated development in plants.In parallel,plants also transmit low or warm temperature signals to these two regulatory modules that precisely modulate the responsive-ness of low or warm temperatures.The core component of circadian clock ELF3 integrates signals from light and warm temperatures to regulate physiological and developmental processes in plants.In this review,we summarize and discuss recent advances and progresses on PIFs-,COP1-HY5-and ELF3-mediated light,low or warm temperature signaling,and highlight emerging insights regarding the interactions between light and low or warm temperature signal transduction pathways in the control of plant growth.
