AIM:To report that Lpcat1 plays an important role in regulating lipopolysaccharide (LPS) inducible gene tran-scription. METHODS:Gene expression in Murine Lung Epithelial MLE-12 cells with LPS treatment or Haemophilus ...AIM:To report that Lpcat1 plays an important role in regulating lipopolysaccharide (LPS) inducible gene tran-scription. METHODS:Gene expression in Murine Lung Epithelial MLE-12 cells with LPS treatment or Haemophilus influenza and Escherichia coli infection was analyzed by employing quantitative Reverse Transcription Polymerase Chain Reaction techniques. Nucleofection was used to deliver Lenti-viral system to express or knock down Lpcat1 in MLE cells. Subcellular protein fractionation and Western blotting were utilized to study Lpcat1 nuclear relocation. RESULTS:Lpcat1 translocates into the nucleus from thecytoplasm in murine lung epithelia (MLE) after LPS treatment. Haemophilus influenza and Escherichia coli , two LPS-containing pathogens that cause pneumonia, triggered Lpcat1 nuclear translocation from the cytoplasm. The LPS inducible gene expression profile was determined by quantitative reverse transcription polymerase chain reaction after silencing Lpcat1 or overexpression of the enzyme in MLE cells. We detected that 17 out of a total 38 screened genes were upregulated, 14 genes were suppressed, and 7 genes remained unchanged in LPS treated cells in comparison to controls. Knockdown of Lpcat1 by shRNA dramatically changed the spectrum of the LPS inducible gene transcription, as 18 genes out of 38 genes were upregulated, of which 20 genes were suppressed or unchanged. Notably, in Lpcat1 overex-pressed cells, 25 genes out of 38 genes were reduced in the setting of LPS treatment.CONCLUSION:These observations suggest that Lpcat1 relocates into the nucleus in response to bacterial infection to differentially regulate gene transcriptional repression.展开更多
In this research, an unusually dimeric G-quadruplex of d（GGGTGGGTGGGTGGGT） （SI）, the potent nanomolar HIV-1 integrase inhibitor, was detected by nuclear magnetic resonance （NMR）. This result has been confirmed b...In this research, an unusually dimeric G-quadruplex of d（GGGTGGGTGGGTGGGT） （SI）, the potent nanomolar HIV-1 integrase inhibitor, was detected by nuclear magnetic resonance （NMR）. This result has been confirmed by electrospray ionization mass spectrometry （ESI-MS） and circular dichroism （CD）.展开更多
Background:Lymphatic metastasis is one of the most common metastatic routes and indicates a poor prognosis in clear-cell renal cell carcinoma(ccRCC).N-acetyltransferase 10(NAT10)is known to catalyze N4-acetylcytidine(...Background:Lymphatic metastasis is one of the most common metastatic routes and indicates a poor prognosis in clear-cell renal cell carcinoma(ccRCC).N-acetyltransferase 10(NAT10)is known to catalyze N4-acetylcytidine(ac4C)modification of mRNA and participate in many cellular processes.However,its role in the lymphangiogenic process of ccRCC has not been reported.This study aimed to elucidate the role of NAT10 in ccRCC lymphangiogenesis,providing valuable insights into potential therapeutic targets for intervention.Methods:ac4C modification and NAT10 expression levels in ccRCC were assessed using public databases and clinical samples.Functional investigations involved manipulating NAT10 expression in cellular and mouse models to study its role in ccRCC.Mechanistic insights were gained through a combination of RNA sequencing,mass spectrometry,co-immunoprecipitation,RNA immuno-precipitation,immunofluorescence,and site-specific mutation analyses.Results:We found that ac4C modification and NAT10 expression levels increased in ccRCC.NAT10 promoted tumor progression and lymphangiogene-sis of ccRCC by enhancing the nuclear import of Yes1-associated transcriptional regulator(YAP1).Subsequently,we identified ankyrin repeat and zinc fin-ger peptidyl tRNA hydrolase 1(ANKZF1)as the functional target of NAT10,and its upregulation in ccRCC was caused by NAT10-mediated ac4C modifi-cation.Mechanistic analyses demonstrated that ANKZF1 interacted with tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon(YWHAE)to competitively inhibit cytoplasmic retention of YAP1,leading to transcriptional activation of pro-lymphangiogenic factors.Conclusions:These results suggested a pro-cancer role of NAT10-mediated acetylation in ccRCC and identified the NAT10/ANKZF1/YAP1 axis as an under-reported pathway involving tumor progression and lymphangiogenesis in ccRCC.展开更多
It is recognized that HIV-1 capsid cores are disassembled in the cytoplasm, releasing their genomes into the nucleus through nuclear pores, but there is also evidence showing the capsid(CA) exists in the nucleus. Whet...It is recognized that HIV-1 capsid cores are disassembled in the cytoplasm, releasing their genomes into the nucleus through nuclear pores, but there is also evidence showing the capsid(CA) exists in the nucleus. Whether HIV-1 enters the nucleus and how it enters the nucleus through the undersized nuclear pore remains mysterious. Based on multicolor labeling and real-time imaging of the viral and cellular components, our observations via light and electron microscopy suggest that HIV-1 selectively gathered at the microtubule organization center(MTOC), leading the nearby nuclear envelope(NE) to undergo deformation,invagination and restoration to form a nuclear vesicle in which the viral particles were wrapped;then, the inner membrane of the nuclear vesicle ruptured to release HIV-1 into the nucleus. This unexpected discovery expands our understanding of the complexity of HIV-1 nuclear entry, which may provide new insights to HIV-1 virology.展开更多
Human immunodeficiency virus-1 capsid(HIV-1 CA) is involved in different stages of the viral replication cycle. During virion assembly, CA drives the formation of the hexameric lattice in immature viral particles, whi...Human immunodeficiency virus-1 capsid(HIV-1 CA) is involved in different stages of the viral replication cycle. During virion assembly, CA drives the formation of the hexameric lattice in immature viral particles, while in mature virions CA monomers assemble in cone-shaped cores surrounding the viral RNA genome and associated proteins. In addition to its functions in late stages of the viral replication cycle, CA plays key roles in a number of processes during early phases of HIV-1 infection including trafficking, uncoating, recognition by host cellular proteins and nuclear import of the viral preintegration complex. As a result of efficient cooperation of CA with other viral and cellular proteins, integration of the viral genetic material into the host genome, which is an essential step for productive viral infection, successfully occurs. In this review, we will summarize available data on CA functions in HIV-1 replication, describing in detail its roles in late and early phases of the viral replication cycle.展开更多
Both thymocytes and tumor cells express M2 type isoenzyme of pyruvate kinase(M2PK),which is different from R type isoenzyme of pyruvate kinase(RPK)that is expressed in erythrocytes.In this report,the effect of RPK and...Both thymocytes and tumor cells express M2 type isoenzyme of pyruvate kinase(M2PK),which is different from R type isoenzyme of pyruvate kinase(RPK)that is expressed in erythrocytes.In this report,the effect of RPK and M2PK on the transcription of human immunodeficiency virus type 1(HIV-1)was tested.The results indicated that M2PK could enhance HIV-1 transcription from its long terminal repeat(LTR)promoter,while RPK did not have such an effect.Specific down-regulation of M2PK could inhibit HIV-1 transcription from its LTR region.Furthermore,it was found that the C terminal region of M2PK is responsible for this effect.Collectively,the cellular factor M2PK that is expressed in thymocytes could facilitate the transcription of HIV-1.展开更多
To control gene expression by directly responding to hormone concentrations, both animal and plant cells have exploited comparable mechanisms to sense small-molecule hormones in nucleus. Whether nuclear entry of these...To control gene expression by directly responding to hormone concentrations, both animal and plant cells have exploited comparable mechanisms to sense small-molecule hormones in nucleus. Whether nuclear entry of these hormones is actively transported or passively diffused, as conventionally postulated, through the nuclear pore complex, remains enigmatic. Here, we identified and characterized a jasmonate transporter in Arabidopsis thaliana, AtJAT1/AtABCG16, which exhibits an unexpected dual localization at the nuclear envelope and plasma membrane. We show that AtJAT1/AtABCG16 controls the cytoplasmic and nuclear partition of jasmonate phytohormones by mediating both cellular efflux of jasmonic acid （JA） and nuclear influx of jasmonoyl-isoleucine （JA-Ile）, and is essential for maintaining a critical nuclear JA-Ile concentration to activate JA signaling. These results illustrate that transporter-mediated nuclear entry of small hormone molecules is a new mechanism to regulate nuclear hormone signaling. Our findings provide an avenue to develop pharmaceutical agents targeting the nuclear entry of small molecules.展开更多
基金Supported by A United States National Institutes of Health R01 grant HL091916 to Zhao Yan American Heart Association grant 12SDG12040330 to Zou C, in part
文摘AIM:To report that Lpcat1 plays an important role in regulating lipopolysaccharide (LPS) inducible gene tran-scription. METHODS:Gene expression in Murine Lung Epithelial MLE-12 cells with LPS treatment or Haemophilus influenza and Escherichia coli infection was analyzed by employing quantitative Reverse Transcription Polymerase Chain Reaction techniques. Nucleofection was used to deliver Lenti-viral system to express or knock down Lpcat1 in MLE cells. Subcellular protein fractionation and Western blotting were utilized to study Lpcat1 nuclear relocation. RESULTS:Lpcat1 translocates into the nucleus from thecytoplasm in murine lung epithelia (MLE) after LPS treatment. Haemophilus influenza and Escherichia coli , two LPS-containing pathogens that cause pneumonia, triggered Lpcat1 nuclear translocation from the cytoplasm. The LPS inducible gene expression profile was determined by quantitative reverse transcription polymerase chain reaction after silencing Lpcat1 or overexpression of the enzyme in MLE cells. We detected that 17 out of a total 38 screened genes were upregulated, 14 genes were suppressed, and 7 genes remained unchanged in LPS treated cells in comparison to controls. Knockdown of Lpcat1 by shRNA dramatically changed the spectrum of the LPS inducible gene transcription, as 18 genes out of 38 genes were upregulated, of which 20 genes were suppressed or unchanged. Notably, in Lpcat1 overex-pressed cells, 25 genes out of 38 genes were reduced in the setting of LPS treatment.CONCLUSION:These observations suggest that Lpcat1 relocates into the nucleus in response to bacterial infection to differentially regulate gene transcriptional repression.
基金the National Natural Science Foundation of China(No.20472009)the Research Fund for the Doctoral Program of Higher Education.
文摘In this research, an unusually dimeric G-quadruplex of d（GGGTGGGTGGGTGGGT） （SI）, the potent nanomolar HIV-1 integrase inhibitor, was detected by nuclear magnetic resonance （NMR）. This result has been confirmed by electrospray ionization mass spectrometry （ESI-MS） and circular dichroism （CD）.
基金This study was supported by the National Natural Sci-ence Foundation of China(81874090,81972630,82202911,82300786).
文摘Background:Lymphatic metastasis is one of the most common metastatic routes and indicates a poor prognosis in clear-cell renal cell carcinoma(ccRCC).N-acetyltransferase 10(NAT10)is known to catalyze N4-acetylcytidine(ac4C)modification of mRNA and participate in many cellular processes.However,its role in the lymphangiogenic process of ccRCC has not been reported.This study aimed to elucidate the role of NAT10 in ccRCC lymphangiogenesis,providing valuable insights into potential therapeutic targets for intervention.Methods:ac4C modification and NAT10 expression levels in ccRCC were assessed using public databases and clinical samples.Functional investigations involved manipulating NAT10 expression in cellular and mouse models to study its role in ccRCC.Mechanistic insights were gained through a combination of RNA sequencing,mass spectrometry,co-immunoprecipitation,RNA immuno-precipitation,immunofluorescence,and site-specific mutation analyses.Results:We found that ac4C modification and NAT10 expression levels increased in ccRCC.NAT10 promoted tumor progression and lymphangiogene-sis of ccRCC by enhancing the nuclear import of Yes1-associated transcriptional regulator(YAP1).Subsequently,we identified ankyrin repeat and zinc fin-ger peptidyl tRNA hydrolase 1(ANKZF1)as the functional target of NAT10,and its upregulation in ccRCC was caused by NAT10-mediated ac4C modifi-cation.Mechanistic analyses demonstrated that ANKZF1 interacted with tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon(YWHAE)to competitively inhibit cytoplasmic retention of YAP1,leading to transcriptional activation of pro-lymphangiogenic factors.Conclusions:These results suggested a pro-cancer role of NAT10-mediated acetylation in ccRCC and identified the NAT10/ANKZF1/YAP1 axis as an under-reported pathway involving tumor progression and lymphangiogenesis in ccRCC.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29050100)。
文摘It is recognized that HIV-1 capsid cores are disassembled in the cytoplasm, releasing their genomes into the nucleus through nuclear pores, but there is also evidence showing the capsid(CA) exists in the nucleus. Whether HIV-1 enters the nucleus and how it enters the nucleus through the undersized nuclear pore remains mysterious. Based on multicolor labeling and real-time imaging of the viral and cellular components, our observations via light and electron microscopy suggest that HIV-1 selectively gathered at the microtubule organization center(MTOC), leading the nearby nuclear envelope(NE) to undergo deformation,invagination and restoration to form a nuclear vesicle in which the viral particles were wrapped;then, the inner membrane of the nuclear vesicle ruptured to release HIV-1 into the nucleus. This unexpected discovery expands our understanding of the complexity of HIV-1 nuclear entry, which may provide new insights to HIV-1 virology.
基金supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIHthe Intramural AIDS Targeted Antiviral Program+4 种基金supported by National Natural Science Foundation of China (No. 31770188)Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29010000)the National Science and Technology Major Project (No. 2018ZX10101004)the Special major program of Wuhan Institute of Virology (No. WIV-135-TP1)the Hundred Talents Program of Chinese Academy of Sciences, and the State Key Laboratory of Virology open projects (No. 2017IOV003)
文摘Human immunodeficiency virus-1 capsid(HIV-1 CA) is involved in different stages of the viral replication cycle. During virion assembly, CA drives the formation of the hexameric lattice in immature viral particles, while in mature virions CA monomers assemble in cone-shaped cores surrounding the viral RNA genome and associated proteins. In addition to its functions in late stages of the viral replication cycle, CA plays key roles in a number of processes during early phases of HIV-1 infection including trafficking, uncoating, recognition by host cellular proteins and nuclear import of the viral preintegration complex. As a result of efficient cooperation of CA with other viral and cellular proteins, integration of the viral genetic material into the host genome, which is an essential step for productive viral infection, successfully occurs. In this review, we will summarize available data on CA functions in HIV-1 replication, describing in detail its roles in late and early phases of the viral replication cycle.
基金This work was supported by the National Basic Research Program of China(973 Program)(No.2006CB504305)National Special Research Program of Major Infectious Diseases(No.2008ZX10001-002)the 111 Project(No.B06018).
文摘Both thymocytes and tumor cells express M2 type isoenzyme of pyruvate kinase(M2PK),which is different from R type isoenzyme of pyruvate kinase(RPK)that is expressed in erythrocytes.In this report,the effect of RPK and M2PK on the transcription of human immunodeficiency virus type 1(HIV-1)was tested.The results indicated that M2PK could enhance HIV-1 transcription from its long terminal repeat(LTR)promoter,while RPK did not have such an effect.Specific down-regulation of M2PK could inhibit HIV-1 transcription from its LTR region.Furthermore,it was found that the C terminal region of M2PK is responsible for this effect.Collectively,the cellular factor M2PK that is expressed in thymocytes could facilitate the transcription of HIV-1.
文摘To control gene expression by directly responding to hormone concentrations, both animal and plant cells have exploited comparable mechanisms to sense small-molecule hormones in nucleus. Whether nuclear entry of these hormones is actively transported or passively diffused, as conventionally postulated, through the nuclear pore complex, remains enigmatic. Here, we identified and characterized a jasmonate transporter in Arabidopsis thaliana, AtJAT1/AtABCG16, which exhibits an unexpected dual localization at the nuclear envelope and plasma membrane. We show that AtJAT1/AtABCG16 controls the cytoplasmic and nuclear partition of jasmonate phytohormones by mediating both cellular efflux of jasmonic acid （JA） and nuclear influx of jasmonoyl-isoleucine （JA-Ile）, and is essential for maintaining a critical nuclear JA-Ile concentration to activate JA signaling. These results illustrate that transporter-mediated nuclear entry of small hormone molecules is a new mechanism to regulate nuclear hormone signaling. Our findings provide an avenue to develop pharmaceutical agents targeting the nuclear entry of small molecules.
