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Search Results: 1 - 10 of 14263 matches for " Beifen Shen "
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PI3-K/Akt pathway contributes to IL-6-dependent growth of 7TD1 cells
JiYan Zhang, Yan Li, BeiFen Shen
Cancer Cell International , 2003, DOI: 10.1186/1475-2867-3-1
Abstract: We investigated the activation status of Akt in 7TD1 cells induced by IL-6. With PI 3-K specific inhibitor wortmannin, we also investigated the biological roles of Akt activation in 7TD1 cells.IL-6 stimulated phosphorylation of Akt in a dose- and time-dependent manner in 7TD1 cells. Wortmannin significantly reduced IL-6-induced phosphorylation of Akt and IL-6-dependent growth of 7TD1 cells. Furthermore, wortmannin blocked IL-6-induced up-regulation of XIAP, but not Bcl-2 in 7TD1 cells.The data suggest that IL-6-induced PI 3-K/Akt activation is essential for the optimal growth of 7TD1 cells through up-regulation of anti-apoptosis proteins such as XIAP.Interleukin-6 (IL-6) is a pleiotropic cytokine. The binding of IL-6 to its receptor induces the activation of multiple signal transduction pathways such as JAK/STATs (Janus tyrosine kinase/signal transducers and activators of transcription) pathway, Ras/ERK (extracellular signal-regulated kinase) pathway, and PI 3-K (phosphotidylinositol 3-kinase)/Akt pathway via gp130 tyrosine phosphorylation [1]. The roles of JAK/STATs pathway and Ras/ERK pathway in the biological effects of IL-6 have been extensively investigated [1,2]. However, what role PI 3-K/Akt plays in IL-6 signaling is less clear. Akt is a serine (Ser)/threonine (Thr) protein kinase which resides within the cytosol in a catalytically inactive state in quiescent or serum-starved cells. After stimulation of cells with growth factors and cytokines, Akt is catalytically activated by phosphorylation at Thr308 and Ser473. Activated Akt in turn phosphorylates downstream target molecules and induces the expression of anti-apoptosis proteins, which promote induction of its anti-apoptosis effect [3]. Recently, growing evidence suggests the involvement of PI 3-K/Akt in IL-6-dependent survival and proliferative responses in several types of cells [3-6]. Still, whether PI 3-K/Akt plays the same role in IL-6-dependent growth of 7TD1 mouse-mouse B cell hybridoma is not known
Protein kinase ERK contributes to differential responsiveness of human myeloma cell lines to IFNα
Lun Song, Yan Li, Beifen Shen
Cancer Cell International , 2002, DOI: 10.1186/1475-2867-2-9
Abstract: Sko-007 is a myeloma cell line whose growth is arrested by IFNα; however, IFNα promoted the proliferation of the other myeloma cell line U266. We observed that the growth-stimulation effect of IFNα on U266 cells did not result from up-regulation of the IL-6 receptors on cell surface; while IFNα treatment on Sko-007 cells significantly reduced gp130 expression. Moreover, the transcription factors STAT3 and STAT1, which are involved in the JAK/STAT signal transduction pathway, can be activated in both IFNα-stimulated and -inhibited myeloma cell lines; while the activation of the protein kinase ERK, which is involved in the Ras/MAPK signal transduction pathway, can be down-regulated in IFNα-arrested Sko-007 cells and up-regulated in IFNα-stimulated U266 cells. In addition, both IFNα-induced growth-stimulation effect and the up-regulated activation of ERK in U266 cells were efficiently inhibited by PD98059, the specific inhibitor of MAPK/ERK kinase (MEK).Myeloma cells responsiveness to IFNα is heterogeneous and the activation state of ERK in the Ras/MAPK signalling pathway mainly contributed to this difference.The typically growth-inhibitory action of Interferonα (IFNα) has made it a commonly used therapeutic agent in the treatment of a wide variety of human malignancies, including multiple myeloma (MM) [1]. However, although a considerable number of the clinical trials have addressed the effectiveness of IFNα on MM therapy [2], other reports also showed that in some MM patients, IFNα can promote the proliferation of myeloma cells in vivo and result in the development of aggressive plasma cell leukemia (PCL) [3]. Therefore, the action of IFNα on MM cell growth is a matter of debate, and the mechanism of this discrepancy is the topic of this study.Interleukin-6 (IL-6) is the major growth and survival factor for myeloma cells. IFNα and IL-6 clearly use distinct receptor complexes; however, both cytokines have been shown to use two common signal transduction pathways to me
Prediction on the binding domain between human interleukin-6 and its receptor
Jiannan Feng,Yunfang Ren,Beifen Shen
Science China Life Sciences , 2000, DOI: 10.1007/BF02879306
Abstract: Based on the spatial conformations of human interleukin-6 (hIL-6) derived from nuclear magnetic resonance analysis and human interleukin-6 receptor (hIL-6R) modeled with homology modeling method using human growth hormone receptor as template, the interaction between hIL-6 and its receptor (hIL-6R) is studied with docking program according to the surface electrostatic potential analysis and spatial conformation complement. The stable region structure composed of hIL-6 and hIL-6R is obtained on the basis of molecular mechanism optimization and molecular dynamics simulation. The binding domain between hIL-6 and hIL-6R is predicted theoretically. Furthermore, the especial binding sites that influence the interaction between hIL-6 and hIL-6R are confirmed. The results lay a theoretical foundation for confirming the active regions of hIL-6 and designing novel antagonist with computer-guided techniques.
Identification of binding epitope of a monoclonal antibody (Z12) against human TNF-α using computer modeling and deletion mutant technique
Wei Zhang,Jiannan Feng,Beifen Shen
Science China Life Sciences , 2004, DOI: 10.1007/BF03182773
Abstract: The genes of the heavy and light chain variable region (VH, VL) of Z12 antibody against hTNF-α were cloned, and according to the translated sequence of amino acids, the spatial structures of VH and VL domains were modeled by using homology-based modeling method, followed by constructing the whole three-dimensional structure of Fv fragment. The complex model of Fv interacting with hTNF-α was gained with computer-guided molecular docking method, based on which, it was predicted that the epitope recognized by Z12 was from 141 to 146 of hTNF-α. hTNF-α molecule was divided into two fragments of N-terminal region from 1 to 91 and C-terminal region from 92 to 157 with prokaryotic expression. The measured results suggested that the antigenic epitope recognized by Z12 antibody was located in the C-terminal region 92–157 of hTNF-α, proving the predicted result reliable preliminarily. Further experimental results showed that after hTNF-α 141–146 residues were deleted, Z12 antibody almost lost the ability to recognize the mutant, suggesting that the amino acid residues from 141 to 146 of hTNF-α were specially recognized by Z12 antibody.
Initial function analysis of a novel erythroid differentiation related geneEDRF1
Duncheng Wang,Yan Li,Beifen Shen
Science China Life Sciences , 2001, DOI: 10.1007/BF02882391
Abstract: Erythroid differentiation depends on the establishment of specific patterns of gene expression. Hypersensitive site 2 (HS2, serving as a major enhancer of globin genes)-binding proteins may be involved in its natural open chromosomal environment formation. Previously we prepared monoclonal antibodies against HS2-binding nuclear proteins of terminal differentiated erythroid cells. By utilizing the monoclonal antibodies, we screened λ-gt11 human fetal liver cDNA expression library and obtained one cDNA clone, which was named erythroid differentiation related gene (EDRF1, Genbank accession number AF040247), encompassing an entire open reading frame. We investigated the expression pattern ofEDRF1 by RT-PCR technique. And a clue to the function ofEDRF1 has been found from confirmation of high levels ofEDRF1 mRNA in differentiated K562 and human fetal liver tissue. To illuminate the function ofEDRF1 in K562 cells, sense and antisenseEDRF1 constructs were prepared and transfected into K562 cells. α-globin mRNA was down-regulated and EpoR (erythropoietin receptor) mRNA expression was increased in antisense transfected cells. Cells transfected with sense construct grew more slowly than control cells suggested by [3H] thimidine incorporation experiments. Suppression of K562 proliferation was accompanied by increased spontaneous hemoglobin synthesis demonstrated by spectrometry. K562 cells transfected with sense construct exhibited reduced clongenicity compared with control cells in methycellulose culture. These data provided the evidence thatEDRF1 can influence globin expression and hemoglobin synthesis in K562 cells and modulated self-renewal in K562 cells.
A novel erythroid differentiation related gene EDRF2 inhibited α-globin gene expression in K562 cells
Duncheng Wang,Xiaoming Yang,Beifen Shen
Chinese Science Bulletin , 2002, DOI: 10.1360/02tb9093
Abstract: In previous studies, we found that EDRF2 was an erythroid differentiation related factor, whose expression was markedly upregulated during erythroid differentiation. It suggested that this factor played a role in erythropoiesis. By using rapid amplification of cDNA ends technology, we cloned EDRF2 gene 5 ′- and 3 ′-cDNA ends successfully. Transfection and Northern blot analysis demonstrated that EDRF2 inhibited mRNA expression of a-globin gene, while did not regulate γ-globin gene expression. Gel shift assay confirmed that DNA-binding activity of erythroid specific transcription factors GATA-1, NF-E2 and AP1 was not affected by either forced overexpression or artificial downregulation of EDRF2 gene in K562 cells. However, we detected that the negative regulator of expression of GATA-1 transcription factor was increased in EDRF2 overexpressed K562 cells. These results strongly suggested that EDRF2 was involved in a-globin gene expression and erythroid differentiation and served as a negative regulator of PU.1 transcription factor.
Initial function analysis of a novel erythroid differentiation related geneEDRF1

Duncheng Wang,Yan Li,Beifen Shen,

中国科学C辑(英文版) , 2001,
Abstract: Erythroid differentiation depends on the establishment of specific patterns of gene expression. Hypersensitive site 2 (HS2, serving as a major enhancer of globin genes)-binding proteins may be involved in its natural open chromosomal environment formation. Previously we prepared monoclonal antibodies against HS2-binding nuclear proteins of terminal differentiated erythroid cells. By utilizing the monoclonal antibodies, we screened λ-gt11 human fetal liver cDNA expression library and obtained one cDNA clone, which was named erythroid differentiation related gene (EDRF1, Genbank accession number AF040247), encompassing an entire open reading frame. We investigated the expression pattern ofEDRF1 by RT-PCR technique. And a clue to the function ofEDRF1 has been found from confirmation of high levels ofEDRF1 mRNA in differentiated K562 and human fetal liver tissue. To illuminate the function ofEDRF1 in K562 cells, sense and antisenseEDRF1 constructs were prepared and transfected into K562 cells. α-globin mRNA was down-regulated and EpoR (erythropoietin receptor) mRNA expression was increased in antisense transfected cells. Cells transfected with sense construct grew more slowly than control cells suggested by 3H] thimidine incorporation experiments. Suppression of K562 proliferation was accompanied by increased spontaneous hemoglobin synthesis demonstrated by spectrometry. K562 cells transfected with sense construct exhibited reduced clongenicity compared with control cells in methycellulose culture. These data provided the evidence thatEDRF1 can influence globin expression and hemoglobin synthesis in K562 cells and modulated self-renewal in K562 cells.
Identification of binding epitope of a monoclonal antibody (Z12) against human TNF-alpha using computer modeling and deletion mutant technique.
Identification of binding epitope of a monoclonal antibody (Z12) against human TNF-α using computer modeling and deletion mutant technique

ZHANG Wei,FENG Jiannan,SHEN Beifen,

中国科学C辑(英文版) , 2004,
Abstract: The genes of the heavy and light chain variable region (VH, VL) of Z12 antibody against hTNF-alpha were cloned, and according to the translated sequence of amino acids, the spatial structures of VH and VL domains were modeled by using homology-based modeling method, followed by constructing the whole three-dimensional structure of Fv fragment. The complex model of Fv interacting with hTNF-alpha was gained with computer-guided molecular docking method, based on which, it was predicted that the epitope recognized by Z12 was from 141 to 146 of hTNF-alpha. hTNF-alpha molecule was divided into two fragments of N-terminal region from 1 to 91 and C-terminal region from 92 to 157 with prokaryotic expression. The measured results suggested that the antigenic epitope recognized by Z12 antibody was located in the C-terminal region 92-157 of hTNF-alpha, proving the predicted result reliable preliminarily. Further experimental results showed that after hTNF-a 141-146 residues were deleted, Z12 antibody almost lost the ability to recognize the mutant, suggesting that the amino acid residues from 141 to 146 of hTNF-alpha were specially recognized by Z12 antibody.
Selective unresponsiveness to the inhibition of p38 MAPK activation by cAMP helps L929 fibroblastoma cells escape TNF-α-induced cell death
Jing Wang, Ruihong Tang, Ming Lv, Jiyan Zhang, Beifen Shen
Molecular Cancer , 2010, DOI: 10.1186/1476-4598-9-6
Abstract: Intracellular cAMP was determined in L929 fibroblastoma cells after treatment of the cells with various cAMP elevation agents. Effects of cAMP in the presence or absence of the RNA synthesis inhibitor actinomycin D or small interfering RNAs (siRNAs) against CREB on TNF-α-induced cell death in L929 cells were measured by propidium iodide (PI) staining and subsequent flow cytomety. The activation of p38 and c-Jun N-terminal protein kinase (JNK), another member of MAPK superfamily, was analyzed by immunoblotting. JNK selective inhibitor D-JNKi1 and p38 selective inhibitor SB203580 were included to examine the roles of JNK and p38 in this process. The expression of DLC or other mediators of cAMP was analyzed by immunoblotting. After ectopic expression of DLC with a transfection marker GFP, effects of cAMP on TNF-α-induced cell death in GFP+ cells were measured by PI staining and subsequent flow cytomety.Elevation of cAMP suppressed TNF-α-induced necrotic cell death in L929 fibroblastoma cells via CREB-mediated transcription. The pro-survival role of cAMP was associated with selective unresponsiveness of L929 cells to the inhibition of p38 activation by cAMP, even though cAMP significantly inhibited the activation of JNK under the same conditions. Further exploration revealed that the induction of DLC, the major mediator of p38 inhibition by cAMP, was impaired in L929 cells. Enforced inhibition of p38 activation by using p38 specific inhibitor or ectopic expression of DLC reversed the protection of L929 cells by cAMP from TNF-α-induced cell death.These data suggest that the lack of a pro-apoptotic pathway in tumor cells leads to a net survival effect of cAMP.It is known that persistent stress and depression, which leads to continuously elevated levels of stress hormones such as epinephrine, may increase tumor incidence and promote metastatic growth. Cyclic AMP (cAMP) is the first identified intracellular mediator (second messenger) of hormone action. The downstream effec
Active regions’ setting of the extracellular ligandbinding domain of human interleukin-6 receptor
Yunfang Ren,Hong Qu,Jiannan Feng,Song Li,Beifen Shen
Chinese Science Bulletin , 2000, DOI: 10.1007/BF02886075
Abstract: The reliable three dimensional (3-D) structure of the extracellular ligand-binding domain (V106-P322) of human interleukin-6 receptor (hIL-6R) has been constructed by means of computer-guided homology modeling techniques using the crystal structure of the extracellular ligand-binding region (K52–L251) of human growth hormone receptor (hGHR) as templet. The space location of some key residues which influence the combination ability between the receptor and the ligand has been observed and the effects of point mutagenesis of the four conservative cysteine residues on the space conformation are analyzed. The results show that the space conformation of the side-chain carboxyl of E305 plays a key role in the ligand-binding ability. Furthermore, the space conformation of the side-chain carboxyl of E305 is very important for the electrostatic potential complementarity between hIL-6R and hIL-6 according to the docking method.
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