The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to b...The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.展开更多
The history and geographical origin of citron （Citrus medica L.） is still unknown but most of authors agree that it originated in Southeast Asia. There are different opinions about the exact period and the steps by ...The history and geographical origin of citron （Citrus medica L.） is still unknown but most of authors agree that it originated in Southeast Asia. There are different opinions about the exact period and the steps by which it was brought from its country of origin to the Mediterranean basin where it is cultivated in Corsica, Crete and in southern Italy （Calabria region）. In particulary, Citrus medica ＇Diamante＇ grows, almost exclusively, in a restricted area of the Tyrrhenian cost of the region Calabria, called ＂Riviera dei Cedri＂, a relevant local economic district. This citron has been and is, still being used by Jews for worship during the Feast of Tabernacles, a very important religious ritual, where it plays a prominent part; in fact, for this holiday of Sukkot, the use of the authentic citron that grows in Calabria region is recommended, because it is not grafted. In this paper, the fascinating history of C. medica and its spread from the centers of origin to the Mediterranean is reported with the aim to investigate the religious and cultural significance of the C. medica ＇Diamante＇, an exclusive and historical heritage of the Calabria region.展开更多
To study the effect of Green plum citron double strain fermentation filtrate(DSF)on the proliferation rate of HaCaT keratinocytes by CCK8 assay.The effect of DSF on the mRNA transcription levels of filagolin(FLG),lori...To study the effect of Green plum citron double strain fermentation filtrate(DSF)on the proliferation rate of HaCaT keratinocytes by CCK8 assay.The effect of DSF on the mRNA transcription levels of filagolin(FLG),loricrin(LOR),and occludin 1(CLD1)in HaCaT cells in sodium dodecyl sulfate(SLS)model was investigated by qPCR.The effect of DSF on the content of TNF-αin the supernatant of HaCaT cells in the model was investigated by Elisa.The results showed that DSF had no toxicity to HaCaT cells,but it could increase the mRNA transcription levels of FLG,LOR and CLD1 in HaCaT cells in the model,and reduce the content of TNF-αin the supernatant of HaCaT cells in the model.DSF had a certain effect on skin care of strengthening skin barrier.展开更多
Hepatocyte growth factor-regulated tyrosine kinase substrate(Hrs)is a key component of the endosomal sorting complexes required for transport and has been demonstrated to play a regulatory role in endocytosis/exocytos...Hepatocyte growth factor-regulated tyrosine kinase substrate(Hrs)is a key component of the endosomal sorting complexes required for transport and has been demonstrated to play a regulatory role in endocytosis/exocytosis and the accumulation of internal vesicles in multivesicular bodies.Citron kinase is a Ser/The kinase that we previously reported to enhance human immunodeficiency virus type 1(HIV-1)virion production.However,the relationship between Hrs and citron kinase in HIV-1 production remains elusive.Here,we report that Hrs interacts with citron kinase via its FYVE domain.Overexpression of Hrs or the FYVE domain resulted in a significant decrease in HIV-1 virion production.Depletion of Hrs by RNA interference in HEK293T cells increased HIV-1 virion production and enhanced the activity of citron kinase.These data suggest that Hrs inhibits HIV-1 production by inhibiting citron kinase-mediated exocytosis.展开更多
The inhibitory effect of large tumor suppressor kinase(LATS1/2)on the activity of the oncoprotein yes-associated protein(YAP)is crucial to maintain tissue homeostasis.Proteomic studies have identified several new regu...The inhibitory effect of large tumor suppressor kinase(LATS1/2)on the activity of the oncoprotein yes-associated protein(YAP)is crucial to maintain tissue homeostasis.Proteomic studies have identified several new regulators of this process.Recently,citron kinase(CIT)was listed as a potential binding candidate of Hippo-related components,suggesting a new connection between CIT and the Hippo pathway.Aside from CITs role in cytokinesis,the molecular crosstalk between CIT and the Hippo pathway is largely unknown.Here,we demonstrate a role for CIT as a scaffold protein Unking LATS2 and YAP.More importantly,CIT interacts with LATS2 to directly suppress LATS2 phosphorylation at the hydrophobic motif—targeted by MST1,leading to LATS2 inactivation and YAP activation.By studying their genetic interactions,we found that Sticky,the CIT homolog in Drosophila melanogaster,functions with Warts to control Drosophila eye development.Together,our study confirms citron kinase as a novel regulator of the Hippo pathway.展开更多
Citrus canker,caused by Xanthomonas citri subsp.citri(Xcc),is a globally quarantine disease infecting nearly all Citrus cultivars.Citron C-05 has been identified with complete and active resistance to Xcc.However,the ...Citrus canker,caused by Xanthomonas citri subsp.citri(Xcc),is a globally quarantine disease infecting nearly all Citrus cultivars.Citron C-05 has been identified with complete and active resistance to Xcc.However,the mechanism underlying Citron C-05's resistance to Xcc remains elusive.We identified a gene cluster on chromosome 8 of the citrus genome comprising five pathogenesis-related 4-like genes.PR4A was upregulated in Citron C-05 leaves under Xcc infection,exhibiting the highest expression among these PR4-like genes.In addition,PR4A expression was higher in leaves of disease-resistant genotypes than susceptible genotypes under Xcc invasion.Bimolecular fluorescence complementation(BiFC)and Split-Luc assays indicated that CmWRKY75,a positive regulator of PR4A,interacted with pthA4 and upregulated expression of PR4A in Citron C-05 leaves.Regulatory function for the expression of CmPR4A was localized to a 516-nucleotide region upstream of the translational start site,which was designated Pro CmPR4A-P516.Transient overexpression of CmPR4A improved resistance to Xcc in sweet orange,and three transgenic lines of OE-CmPR4A exhibited resistance to Pseudomonas syringae pv.tomato DC3000(Pst DC3000)in Arabidopsis.Furthermore,CmSMU2 was identified through yeast two-hybrid library using CmPR4A as bait,Bi FC and Split-Luc assays further verified their interaction.Transient overexpression of CmSMU2 in sweet orange increased resistance to Xcc.Co-expression of CmSMU2 and CmPR4A enhanced accumulation of reactive oxygen species compared to CmSMU2 or CmPR4A,indicating that they may synergistically enhance resistance to Xcc in citrus.These findings lay the groundwork for a theoretical analysis of the mechanism underlying the resistance of Citron C-05 against citrus canker.展开更多
基金supported by the TARCC,Welch Foundation Award(I-1724)the Decherd Foundationthe Pape Adams Foundation,NIH grants NS092616,NS127375,NS117065,NS111776。
文摘The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.
文摘The history and geographical origin of citron （Citrus medica L.） is still unknown but most of authors agree that it originated in Southeast Asia. There are different opinions about the exact period and the steps by which it was brought from its country of origin to the Mediterranean basin where it is cultivated in Corsica, Crete and in southern Italy （Calabria region）. In particulary, Citrus medica ＇Diamante＇ grows, almost exclusively, in a restricted area of the Tyrrhenian cost of the region Calabria, called ＂Riviera dei Cedri＂, a relevant local economic district. This citron has been and is, still being used by Jews for worship during the Feast of Tabernacles, a very important religious ritual, where it plays a prominent part; in fact, for this holiday of Sukkot, the use of the authentic citron that grows in Calabria region is recommended, because it is not grafted. In this paper, the fascinating history of C. medica and its spread from the centers of origin to the Mediterranean is reported with the aim to investigate the religious and cultural significance of the C. medica ＇Diamante＇, an exclusive and historical heritage of the Calabria region.
文摘To study the effect of Green plum citron double strain fermentation filtrate(DSF)on the proliferation rate of HaCaT keratinocytes by CCK8 assay.The effect of DSF on the mRNA transcription levels of filagolin(FLG),loricrin(LOR),and occludin 1(CLD1)in HaCaT cells in sodium dodecyl sulfate(SLS)model was investigated by qPCR.The effect of DSF on the content of TNF-αin the supernatant of HaCaT cells in the model was investigated by Elisa.The results showed that DSF had no toxicity to HaCaT cells,but it could increase the mRNA transcription levels of FLG,LOR and CLD1 in HaCaT cells in the model,and reduce the content of TNF-αin the supernatant of HaCaT cells in the model.DSF had a certain effect on skin care of strengthening skin barrier.
基金in part supported by grants to Guangxia Gao from the National Natural Science Foundation of China(Grant No.81030030)the Ministry of Science and Technology of China(No.2009zx09501-029).
文摘Hepatocyte growth factor-regulated tyrosine kinase substrate(Hrs)is a key component of the endosomal sorting complexes required for transport and has been demonstrated to play a regulatory role in endocytosis/exocytosis and the accumulation of internal vesicles in multivesicular bodies.Citron kinase is a Ser/The kinase that we previously reported to enhance human immunodeficiency virus type 1(HIV-1)virion production.However,the relationship between Hrs and citron kinase in HIV-1 production remains elusive.Here,we report that Hrs interacts with citron kinase via its FYVE domain.Overexpression of Hrs or the FYVE domain resulted in a significant decrease in HIV-1 virion production.Depletion of Hrs by RNA interference in HEK293T cells increased HIV-1 virion production and enhanced the activity of citron kinase.These data suggest that Hrs inhibits HIV-1 production by inhibiting citron kinase-mediated exocytosis.
文摘The inhibitory effect of large tumor suppressor kinase(LATS1/2)on the activity of the oncoprotein yes-associated protein(YAP)is crucial to maintain tissue homeostasis.Proteomic studies have identified several new regulators of this process.Recently,citron kinase(CIT)was listed as a potential binding candidate of Hippo-related components,suggesting a new connection between CIT and the Hippo pathway.Aside from CITs role in cytokinesis,the molecular crosstalk between CIT and the Hippo pathway is largely unknown.Here,we demonstrate a role for CIT as a scaffold protein Unking LATS2 and YAP.More importantly,CIT interacts with LATS2 to directly suppress LATS2 phosphorylation at the hydrophobic motif—targeted by MST1,leading to LATS2 inactivation and YAP activation.By studying their genetic interactions,we found that Sticky,the CIT homolog in Drosophila melanogaster,functions with Warts to control Drosophila eye development.Together,our study confirms citron kinase as a novel regulator of the Hippo pathway.
基金supported by the National Natural Science Foundation of China(32402500 and 31741110)the Scientific Research Fund of Hunan Provincial Education Department,China(21B0220)。
文摘Citrus canker,caused by Xanthomonas citri subsp.citri(Xcc),is a globally quarantine disease infecting nearly all Citrus cultivars.Citron C-05 has been identified with complete and active resistance to Xcc.However,the mechanism underlying Citron C-05's resistance to Xcc remains elusive.We identified a gene cluster on chromosome 8 of the citrus genome comprising five pathogenesis-related 4-like genes.PR4A was upregulated in Citron C-05 leaves under Xcc infection,exhibiting the highest expression among these PR4-like genes.In addition,PR4A expression was higher in leaves of disease-resistant genotypes than susceptible genotypes under Xcc invasion.Bimolecular fluorescence complementation(BiFC)and Split-Luc assays indicated that CmWRKY75,a positive regulator of PR4A,interacted with pthA4 and upregulated expression of PR4A in Citron C-05 leaves.Regulatory function for the expression of CmPR4A was localized to a 516-nucleotide region upstream of the translational start site,which was designated Pro CmPR4A-P516.Transient overexpression of CmPR4A improved resistance to Xcc in sweet orange,and three transgenic lines of OE-CmPR4A exhibited resistance to Pseudomonas syringae pv.tomato DC3000(Pst DC3000)in Arabidopsis.Furthermore,CmSMU2 was identified through yeast two-hybrid library using CmPR4A as bait,Bi FC and Split-Luc assays further verified their interaction.Transient overexpression of CmSMU2 in sweet orange increased resistance to Xcc.Co-expression of CmSMU2 and CmPR4A enhanced accumulation of reactive oxygen species compared to CmSMU2 or CmPR4A,indicating that they may synergistically enhance resistance to Xcc in citrus.These findings lay the groundwork for a theoretical analysis of the mechanism underlying the resistance of Citron C-05 against citrus canker.
