Current Location:home > Browse

Submitted Date



1. chinaXiv:201605.01740 [pdf]

Aberrantly upregulated TRAP1 is required for tumorigenesis of breast cancer

Zhang, Bo; Wei, Peng; Hao, Junfeng; Zhao, Lijing; Zhang, Fenglin; Wei, Taotao; Wang, Jing; Huang, Zhen; Wei, Peng; Liu, Ying; Tu, Yaping
Subjects: Biology >> Biophysics >> Oncology

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is abnormally expressed in many cancers. In this study, we showed that TRAP1 is aberrantly upregulated in breast tumors compared to control tissues. TRAP1 knockdown downregulates mitochondrial aerobic respiratory, sensitizes cells to lethal stimuli, and inhibited tumor growth in MDA-MB-231 and MCF-7 breast cancer cells in vivo. TRAP1 overexpression, however, enhances the capacity to cope with stress conditions. These evidences suggested that TRAP1 is required for tumorigenesis. We also found that TRAP1 regulates the mitochondrial morphology. Relatively lower TRAP1 levels are associated with the rod-shaped mitochondrial phenotype in invasive and metastatic MDA-MB-231 breast cancer cells; on the contrary, higher TRAP1 levels are associated with the tubular network-shaped mitochondrial phenotype in non-invasive MCF-7 cells. Interestingly, the expression of TRAP1 in human breast cancer specimens inversely correlates with tumor grade. Overexpression of TRAP1 in MDA-MB-231 cells causes mitochondrial fusion, triggers mitochondria to form tubular networks, and suppresses cell migration and invasion in vitro and in vivo. These data link TRAP1-regulated mitochondrial dynamics and function with tumorigenesis of breast cancer and suggested that TRAP1 may therefore be a potential target for breast cancer drug development.

submitted time 2016-05-15 Hits4132Downloads1684 Comment 0

2. chinaXiv:201605.01514 [pdf]

Tristetraprolin Recruits Eukaryotic Initiation Factor 4E2 To Repress Translation of AU-Rich Element-Containing mRNAs

Tao, Xianzun; Gao, Guangxia; Tao, Xianzun
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

Tristetraprolin (TTP) regulates the expression of AU-rich element-containing mRNAs through promoting the degradation and repressing the translation of target mRNA. While the mechanism for promoting target mRNA degradation has been extensively studied, the mechanism underlying translational repression is not well established. Here, we show that TTP recruits eukaryotic initiation factor 4E2 (eIF4E2) to repress target mRNA translation. TTP interacted with eIF4E2 but not with eIF4E. Overexpression of eIF4E2 enhanced TTP-mediated translational repression, and downregulation of endogenous eIF4E2 or overexpression of a truncation mutant of eIF4E2 impaired TTP-mediated translational repression. Overexpression of an eIF4E2 mutant that lost the cap-binding activity also impaired TTP's activity, suggesting that the cap-binding activity of eIF4E2 is important in TTP-mediated translational repression. We further show that TTP promoted eIF4E2 binding to target mRNA. These results imply that TTP recruits eIF4E2 to compete with eIF4E to repress the translation of target mRNA. This notion is supported by the finding that downregulation of endogenous eIF4E2 increased the production of tumor necrosis factor alpha (TNF-alpha) protein without affecting the mRNA levels in THP-1 cells. Collectively, these results uncover a novel mechanism by which TTP represses target mRNA translation.

submitted time 2016-05-12 Hits8649Downloads1516 Comment 0

3. chinaXiv:201605.01488 [pdf]

Crystal structures of the PsbS protein essential for photoprotection in plants

Fan, Minrui; Li, Mei; Liu, Zhenfeng; Cao, Peng; Pan, Xiaowei; Zhang, Hongmei; Zhao, Xuelin; Zhang, Jiping; Chang, Wenrui; Fan, Minrui
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

The photosystem II protein PsbS has an essential role in qE-type nonphotochemical quenching, which protects plants from photodamage under excess light conditions. qE is initiated by activation of PsbS by low pH, but the mechanism of PsbS action remains elusive. Here we report the low-pH crystal structures of PsbS from spinach in its free form and in complex with the qE inhibitor N, N'-dicyclohexylcarbodiimide (DCCD), revealing that PsbS adopts a unique folding pattern, and, unlike other members of the light-harvesting-complex superfamily, it is a noncanonical pigment-binding protein. Structural and biochemical evidence shows that both active and inactive PsbS form homodimers in the thylakoid membranes, and DCCD binding disrupts the lumenal intermolecular hydrogen bonds of the active PsbS dimer. Activation of PsbS by low pH during qE may involve a conformational change associated with altered lumenal intermolecular interactions of the PsbS dimer.

submitted time 2016-05-12 Hits2278Downloads1306 Comment 0

4. chinaXiv:201605.01438 [pdf]

Quantitative proteomics using SILAC: Principles, applications, and developments

Chen, Xiulan; Wei, Shasha; Ji, Yanlong; Guo, Xiaojing; Yang, Fuquan; Chen, Xiulan; Wei, Shasha; Ji, Yanlong; Guo, Xiaojing; Yang, Fuquan; Ji, Yanlong
Subjects: Biology >> Biophysics

SILAC is based on direct addition of selected stable isotope amino acids into the cell culture medium, allowing superior quantitative analysis of the cellular proteome compared to other labeling methods. The great advantages of SILAC lie in its straight-forward implementation, quantitative accuracy, and reproducibility over chemical labeling or label-free quantification strategies, favoring its adoption for proteomic research. SILAC has been widely applied to characterize the proteomic changes between different biological samples, to investigate dynamic changes of protein PTMs, to distinguish specific interacting proteins in interaction proteomic analysis, and to analyze protein turnover in the proteome-wide scale. The present review summarizes the principles of SILAC technology, its applications in biological research, and the present state of this technology.

submitted time 2016-05-12 Hits2397Downloads1531 Comment 0

5. chinaXiv:201605.01427 [pdf]

Murine Gammaherpesvirus 68 ORF48 Is an RTA-Responsive Gene Product and Functions in both Viral Lytic Replication and Latency during In Vivo Infection

Qi, Jing; Han, Chuanhui; Gong, Danyang; Liu, Ping; Zhou, Sheng; Deng, Hongyu; Qi, Jing; Han, Chuanhui; Gong, Danyang; Zhou, Sheng
Subjects: Biology >> Biophysics

Replication and transcription activator (RTA) of gammaherpesvirus is an immediate early gene product and regulates the expression of many downstream viral lytic genes. ORF48 is also conserved among gammaherpesviruses; however, its expression regulation and function remained largely unknown. In this study, we characterized the transcription unit of ORF48 from murine gammaherpesvirus 68 (MHV-68) and analyzed its transcriptional regulation. We showed that RTA activates the ORF48 promoter via an RTA-responsive element (48pRRE). RTA binds to 48pRRE directly in vitro and also associates with ORF48 promoter in vivo. Mutagenesis of 48pRRE in the context of the viral genome demonstrated that the expression of ORF48 is activated by RTA through 48pRRE during de novo infection. Through site-specific mutagenesis, we generated an ORF48-null virus and examined the function of ORF48 in vitro and in vivo. The ORF48-null mutation remarkably reduced the viral replication efficiency in cell culture. Moreover, through intranasal or intraperitoneal infection of laboratory mice, we showed that ORF48 is important for viral lytic replication in the lung and establishment of latency in the spleen, as well as viral reactivation from latency. Collectively, our study identified ORF48 as an RTA-responsive gene and showed that ORF48 is important for MHV-68 replication both in vitro and in vivo. IMPORTANCE The replication and transcription activator (RTA), conserved among gammaherpesviruses, serves as a molecular switch for the virus life cycle. It works as a transcriptional regulator to activate the expression of many viral lytic genes. However, only a limited number of such downstream genes have been uncovered for MHV-68. In this study, we identified ORF48 as an RTA-responsive gene of MHV-68 and mapped the cis element involved. By constructing a mutant virus that is deficient in ORF48 expression and through infection of laboratory mice, we showed that ORF48 plays important roles in different stages of viral infection in vivo. Our study provides insights into the transcriptional regulation and protein function of MHV-68, a desired model for studying gammaherpesviruses.

submitted time 2016-05-12 Hits1721Downloads940 Comment 0

6. chinaXiv:201605.01361 [pdf]

A Novel Transgenic Mouse Line for Tracing MicroRNA-155-5p Activity In Vivo

Phiwpan, Krung; Guo, Jie; Zhang, Wei; Hu, Tanyu; Zhang, Jianhua; Zhou, Xuyu; Phiwpan, Krung; Hu, Tanyu; Boruah, Bhargavi M.
Subjects: Biology >> Biophysics

MicroRNA-155 (miR-155) plays significant role in various physiological processes involving both innate and adaptive immunity. miR-155 expression level changes dynamically during various immune responses. However, current approaches for miR-155 detection at the RNA level do not precisely reflect the real-time activity. Herein, we generated a transgenic mouse line (R26-DTR-155T) for determination of miR-155-5p activity in vivo by inserting miR-155-5p target sequence downstream of a reporter transgene comprising Diphtheria Toxin Receptor and TagBlue fluorescence protein. Using this approach, R26-DTR-155T mice were able to measure variation in levels of miR-155-5p activity in specific cell types of interest. The DTR expression levels were inversely correlated with the endogenous miR-155 expression pattern as detected by quantitative RT-PCR. Our data demonstrate a novel transgenic mouse line which could be useful for tracing miR-155-5p activity in specific cell types through measurement of miR-155-5p activity at single cell level.

submitted time 2016-05-11 Hits1793Downloads1002 Comment 0

7. chinaXiv:201605.01360 [pdf]

Increased Sensitivity of DNA Damage Response-Deficient Cells to Stimulated Microgravity-Induced DNA Lesions

Li, Nan; An, Lili; Hang, Haiying; Li, Nan
Subjects: Biology >> Biophysics

Microgravity is a major stress factor that astronauts have to face in space. In the past, the effects of microgravity on genomic DNA damage were studied, and it seems that the effect on genomic DNA depends on cell types and the length of exposure time to microgravity or simulated microgravity (SMG). In this study we used mouse embryonic stem (MES) and mouse embryonic fibroblast (MEF) cells to assess the effects of SMG on DNA lesions. To acquire the insight into potential mechanisms by which cells resist and/or adapt to SMG, we also included Rad9-deleted MES and Mdc1-deleted MEF cells in addition to wild type cells in this study. We observed significant SMG-induced DNA double strand breaks (DSBs) in Rad9(-/-) MES and Mdc1(-/-) MEF cells but not in their corresponding wild type cells. A similar pattern of DNA single strand break or modifications was also observed in Rad9(-/-) MES. As the exposure to SMG was prolonged, Rad9(-/-) MES cells adapted to the SMG disturbance by reducing the induced DNA lesions. The induced DNA lesions in Rad9(-/-) MES were due to SMG-induced reactive oxygen species (ROS). Interestingly, Mdc1(-/-) MEF cells were only partially adapted to the SMG disturbance. That is, the induced DNA lesions were reduced over time, but did not return to the control level while ROS returned to a control level. In addition, ROS was only partially responsible for the induced DNA lesions in Mdc1(-/-) MEF cells. Taken together, these data suggest that SMG is a weak genomic DNA stress and can aggravate genomic instability in cells with DNA damage response (DDR) defects.

submitted time 2016-05-11 Hits2103Downloads1040 Comment 0

8. chinaXiv:201605.01348 [pdf]

A Portion of Inhibitory Neurons in Human Temporal Lobe Epilepsy are Functionally Upregulated: An Endogenous Mechanism for Seizure Termination

Wen, Bo; Qian, Hao; Feng, Jing; Ge, Rong-Jing; Wang, Jin-Hui; Wen, Bo; Qian, Hao; Wang, Jin-Hui; Ge, Rong-Jing; Xu, Xin; Cui, Zhi-Qiang; Zhu, Ru-Yuan; Pan, Long-Sheng; Lin, Zhi-Pei
Subjects: Biology >> Biophysics >> Neurosciences

Main ProblemEpilepsy is one of the more common neurological disorders. The medication is often ineffective to the patients suffering from intractable temporal lobe epilepsy (TLE). As their seizures are usually self-terminated, the elucidation of the mechanism underlying endogenous seizure termination will help to find a new strategy for epilepsy treatment. We aim to examine the role of inhibitory interneurons in endogenous seizure termination in TLE patients. MethodsWhole-cell recordings were conducted on inhibitory interneurons in seizure-onset cortices of intractable TLE patients and the temporal lobe cortices of nonseizure individuals. The intrinsic property of the inhibitory interneurons and the strength of their GABAergic synaptic outputs were measured. The quantitative data were introduced into the computer-simulated neuronal networks to figure out a role of these inhibitory units in the seizure termination. ResultsIn addition to functional downregulation, a portion of inhibitory interneurons in seizure-onset cortices were upregulated in encoding the spikes and controlling their postsynaptic neurons. A patch-like upregulation of inhibitory neurons in the local network facilitated seizure termination. The upregulations of both inhibitory neurons and their output synapses synergistically shortened seizure duration, attenuated seizure strength, and terminated seizure propagation. ConclusionAutomatic seizure termination is likely due to the fact that a portion of the inhibitory neurons and synapses are upregulated in the seizure-onset cortices. This mechanism may create novel therapeutic strategies to treat intractable epilepsy, such as the simultaneous upregulation of cortical inhibitory neurons and their output synapses.

submitted time 2016-05-11 Hits2784Downloads1324 Comment 0

9. chinaXiv:201605.01347 [pdf]

CD47 blockade triggers T cell-mediated destruction of immunogenic tumors

Liu, Xiaojuan; Xu, Hairong; Peng, Hua; Fu, Yang-Xin; Liu, Xiaojuan; Pu, Yang; Cron, Kyle; Deng, Liufu; Fu, Yang-Xin; Xu, Meng Michelle; Pu, Yang; Cron, Kyle; Deng, Liufu; Kline, Justin; Fu, Yang-Xin; Xu, Meng Michelle; Kline, Justin; Frazier, William A.
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

Macrophage phagocytosis of tumor cells mediated by CD47-specific blocking antibodies has been proposed to be the major effector mechanism in xenograft models. Here, using syngeneic immunocompetent mouse tumor models, we reveal that the therapeutic effects of CD47 blockade depend on dendritic cell but not macrophage cross-priming of T cell responses. The therapeutic effects of anti-CD47 antibody therapy were abrogated in T cell-deficient mice. In addition, the antitumor effects of CD47 blockade required expression of the cytosolic DNA sensor STING, but neither MyD88 nor TRIF, in CD11c(+) cells, suggesting that cytosolic sensing of DNA from tumor cells is enhanced by anti-CD47 treatment, further bridging the innate and adaptive responses. Notably, the timing of administration of standard chemotherapy markedly impacted the induction of antitumor T cell responses by CD47 blockade. Together, our findings indicate that CD47 blockade drives T cell-mediated elimination of immunogenic tumors.

submitted time 2016-05-11 Hits2459Downloads1273 Comment 0

10. chinaXiv:201605.01338 [pdf]

ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells

Zhu, Pingping; Wang, Yanying; Huang, Guanling; Du, Ying; Zhang, Geng; Yan, Xinlong; Xia, Pengyan; Ye, Buqing; Wang, Shuo; Hao, Lu; Wu, Jiayi; Fan, Zusen; He, Lei; Huang, Guanling; Hao, Lu; Wu, Jiayi; Fan, Zusen
Subjects: Biology >> Biophysics

Liver cancer stem cells (CSCs) have been identified and shown to have self-renewal and differentiation properties; however, the biology of these hepatic CSCs remains largely unknown. Here, we analyzed transcriptome gene expression profiles of liver CSCs and non-CSCs from hepatocellular carcinoma (HCC) cells lines and found that the transcription factor (TF) ZIC2 is highly expressed in liver CSCs. ZIC2 was required for the self-renewal maintenance of liver CSCs, as ZIC2 depletion reduced sphere formation and xenograft tumor growth in mice. We determined that ZIC2 acts upstream of the TF OCT4 and that ZIC2 recruits the nuclear remodeling factor (NURF) complex to the OCT4 promoter, thereby initiating OCT4 activation. In HCC patients, expression levels of the NURF complex were consistent with clinical severity and prognosis. Moreover, ZIC2 and OCT4 levels positively correlated to the clinicopathological stages of HCC patients. Altogether, our results indicate that levels of ZIC2, OCT4, and the NURF complex can be detected and used for diagnosis and prognosis prediction of HCC patients. Moreover, these factors may be potential therapeutic targets for eradicating liver CSCs.

submitted time 2016-05-11 Hits2700Downloads1524 Comment 0

123  Last  Go  [3 Pages/ 26 Totals]