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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Korean Society for Biochemistry and Molecular Biology
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Volume & Issues
Volume 49, Issue 8 - Aug 2016
Volume 49, Issue 7 - Jul 2016
Volume 49, Issue 6 - Jun 2016
Volume 49, Issue 5 - May 2016
Volume 49, Issue 4 - Apr 2016
Volume 49, Issue 3 - Mar 2016
Volume 49, Issue 2 - Feb 2016
Volume 49, Issue 1 - Jan 2016
Selecting the target year
A novel model of THO/TREX loading onto target RNAs in metazoan gene expression
Hur, Junho K. ; Chung, Yun Doo ;
BMB Reports , volume 49, issue 7, 2016, Pages 355~356
DOI : 10.5483/BMBRep.2016.49.7.099
The THO/TREX complex consists of several conserved subunits and is required for mRNA export. In metazoans, THO/TREX binds a subset of mRNAs during RNA splicing, and facilitates their nuclear export. How THO/TREX selects RNA targets is, however, incompletely understood. In our recent study, we reported that THO is loaded onto Piwi-interacting RNA (piRNA) precursor transcripts independent of splicing, and facilitates convergent transcription in Drosophila ovary. The precursors are later processed into mature piRNAs, small noncoding RNAs that silence transposable elements (TEs). We observed that piRNAs originating from dual-strand clusters, where precursors are transcribed from both strands, were specifically affected by THO mutation. Analysis of THO-bound RNAs showed enrichment of dual-strand cluster transcripts. Interestingly, THO loading onto piRNA precursors was dependent on Cutoff (Cuff), which comprises the Rhino-Deadlock-Cutoff (RDC) complex that is recruited to dual-strand clusters by recognizing H3K9me3 and licenses convergent transcription from he cluster. We also found that THO mutation affected transcription from dual-strand clusters. Therefore, we concluded that THO/TREX is recruited to dual-strand piRNA clusters, independent of splicing events, via multi-protein interactions with chromatin structure. Then, it facilitates transcription likely by suppressing premature termination to ensure adequate expression of piRNA precursors.
Merlin, a regulator of Hippo signaling, regulates Wnt/β-catenin signaling
Kim, Soyoung ; Jho, Eek-hoon ;
BMB Reports , volume 49, issue 7, 2016, Pages 357~358
DOI : 10.5483/BMBRep.2016.49.7.104
Merlin, encoded by the NF2 gene, is a tumor suppressor that exerts its function via inhibiting mitogenic receptors at the plasma membrane. Although multiple mutations in Merlin have been identified in Neurofibromatosis type II (NF2) disease, its molecular mechanism is not fully understood. Here, we show that Merlin interacts with LRP6 and inhibits LRP6 phosphorylation, a critical step for the initiation of Wnt signaling. We found that treatment of Wnt3a caused phosphorylation of Merlin by PAK1, leading to detachment of Merlin from LRP6 and allowing the initiation of Wnt/β-catenin signaling. A higher level of β-catenin was found in tissues from NF2 patients. Enhanced proliferation and migration caused by knockdown of Merlin in glioblastoma cells were inhibited by suppression of β-catenin. Conclusively, these results suggest that sustained Wnt/β-catenin signaling activity induced by abrogation of Merlin-mediated inhibition of LRP6 phosphorylation might be a cause of NF2 disease.
Forensic DNA methylation profiling from evidence material for investigative leads
Lee, Hwan Young ; Lee, Soong Deok ; Shin, Kyoung-Jin ;
BMB Reports , volume 49, issue 7, 2016, Pages 359~369
DOI : 10.5483/BMBRep.2016.49.7.070
DNA methylation is emerging as an attractive marker providing investigative leads to solve crimes in forensic genetics. The identification of body fluids that utilizes tissue-specific DNA methylation can contribute to solving crimes by predicting activity related to the evidence material. The age estimation based on DNA methylation is expected to reduce the number of potential suspects, when the DNA profile from the evidence does not match with any known person, including those stored in the forensic database. Moreover, the variation in DNA implicates environmental exposure, such as cigarette smoking and alcohol consumption, thereby suggesting the possibility to be used as a marker for predicting the lifestyle of potential suspect. In this review, we describe recent advances in our understanding of DNA methylation variations and the utility of DNA methylation as a forensic marker for advanced investigative leads from evidence materials.
Induction of MAP kinase phosphatase 3 through Erk/MAP kinase activation in three oncogenic Ras (H-, K- and N-Ras)-expressing NIH/3T3 mouse embryonic fibroblast cell lines
Koo, JaeHyung ; Wang, Sen ; Kang, NaNa ; Hur, Sun Jin ; Bahk, Young Yil ;
BMB Reports , volume 49, issue 7, 2016, Pages 370~375
DOI : 10.5483/BMBRep.2016.49.7.256
Ras oncoproteins are small molecular weight GTPases known for their involvement in oncogenesis, which operate in a complex signaling network with multiple effectors. Approximately 25% of human tumors possess mutations in a member of this family. The Raf1/MEK/Erk1/2 pathway is one of the most intensively studied signaling mechanisms. Different levels of regulation account for the inactivation of MAP kinases by MAPK phosphatases in a cell type- and stimuli-dependent manner. In the present study, using three inducible Ras-expressing NIH/3T3 cell lines, we demonstrated that MKP3 upregulation requires the activation of the Erk1/2 pathway, which correlates with the shutdown of this pathway. We also demonstrated, by applying pharmacological inhibitors and effector mutants of Ras, that induction of MKP3 at the protein level is positively regulated by the oncogenic Ras/Raf/MEK/Erk1/2 signaling pathway.
c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration
Ahn, Ji-Hwan ; So, Sang-Pil ; Kim, Na-Young ; Kim, Hyun-Ju ; Yoon, Seung-Yong ; Kim, Dong-Hou ;
BMB Reports , volume 49, issue 7, 2016, Pages 376~381
DOI : 10.5483/BMBRep.2016.49.7.246
Several lines of evidence have revealed that phosphorylation of amyloid precursor protein (APP) at Thr668 is involved in the pathogenesis of Alzheimer's disease (AD). Okadaic acid (OA), a protein phosphatase-2A inhibitor, has been used in AD research models to increase tau phosphorylation and induce neuronal death. We previously showed that OA increased levels of APP and induced accumulation of APP in axonal swellings. In this study, we found that in OA-treated neurons, phosphorylation of APP at Thr668 increased and accumulated in axonal swellings by c-jun N-terminal kinase (JNK), and not by Cdk5 or ERK/MAPK. These results suggest that JNK may be one of therapeutic targets for the treatment of AD.
PEP-1-GSTpi protein enhanced hippocampal neuronal cell survival after oxidative damage
Sohn, Eun Jeong ; Shin, Min Jea ; Kim, Dae Won ; Son, Ora ; Jo, Hyo Sang ; Cho, Su Bin ; Park, Jung Hwan ; Lee, Chi Hern ; Yeo, Eun Ji ; Choi, Yeon Joo ; Yu, Yeon Hee ; Kim, Duk-Soo ; Cho, Sung-Woo ; Kwon, Oh Shin ; Cho, Yong-Jun ; Park, Jinseu ; Eum, Won Sik ; Choi, Soo Young ;
BMB Reports , volume 49, issue 7, 2016, Pages 382~387
DOI : 10.5483/BMBRep.2016.49.7.048
Reactive oxygen species generated under oxidative stress are involved in neuronal diseases, including ischemia. Glutathione S-transferase pi (GSTpi) is a member of the GST family and is known to play important roles in cell survival. We investigated the effect of GSTpi against oxidative stress-induced hippocampal HT-22 cell death, and its effects in an animal model of ischemic injury, using a cell-permeable PEP-1-GSTpi protein. PEP-1-GSTpi was transduced into HT-22 cells and significantly protected against H2O2-treated cell death by reducing the intracellular toxicity and regulating the signal pathways, including MAPK, Akt, Bax, and Bcl-2. PEP-1-GSTpi transduced into the hippocampus in animal brains, and markedly protected against neuronal cell death in an ischemic injury animal model. These results indicate that PEP-1-GSTpi acts as a regulator or an antioxidant to protect against oxidative stress-induced cell death. Our study suggests that PEP-1-GSTpi may have potential as a therapeutic agent for the treatment of ischemia and a variety of oxidative stress-related neuronal diseases.
Methyltransferase and demethylase profiling studies during brown adipocyte differentiation
Son, Min Jeong ; Kim, Won Kon ; Oh, Kyoung-Jin ; Park, Anna ; Lee, Da Som ; Han, Baek Soo ; Lee, Sang Chul ; Bae, Kwang-Hee ;
BMB Reports , volume 49, issue 7, 2016, Pages 388~393
DOI : 10.5483/BMBRep.2016.49.7.062
Although brown adipose tissue is important with regard to energy balance, the molecular mechanism of brown adipocyte differentiation has not been extensively studied. Specifically, regulation factors at the level of protein modification are largely unknown. In this study, we examine the changes in the expression level of enzymes which are involved in protein lysine methylation during brown adipocyte differentiation. Several enzymes, in this case SUV420H2, PRDM9, MLL3 and JHDM1D, were found to be up-regulated. On the other hand, Set7/9 was significantly down-regulated. In the case of SUV420H2, the expression level increased sharply during brown adipocyte differentiation, whereas the expression of SUV420H2 was marginally enhanced during the white adipocyte differentiation. The knock-down of SUV420H2 caused the suppression of brown adipocyte differentiation, as compared to a scrambled control. These results suggest that SUV420H2, a methyltransferase, is involved in brown adipocyte differentiation, and that the methylation of protein lysine is important in brown adipocyte differentiation.
Glioma-Associated Oncogene Homolog1 (Gli1)-Aquaporin1 pathway promotes glioma cell metastasis
Liao, Zheng-qiang ; Ye, Ming ; Yu, Pei-gen ; Xiao, Chun ; Lin, Feng-yun ;
BMB Reports , volume 49, issue 7, 2016, Pages 394~399
DOI : 10.5483/BMBRep.2016.49.7.011
Glioma-Associated Oncogene Homolog1 (Gli1) is known to be activated in malignant glioma; however, its downstream pathway has not been fully explained. The aim of this study was to explore the role of Gli1-Aquaporin1 (AQP1) signal pathway in glioma cell survival. Our data suggests that both Gli1 and AQP1 are upregulated in glioma tissues, as in comparison to in normal tissues. These up-regulation phenomena were also observed in glioma U251 and U87 cells. It was demonstrated that Gli1 positively regulated the AQP1 expression. By luciferase reporter gene and ChIP assay, we observed that this modulation process was realized by combination of Gli1 with AQP1 promotor. In addition, knock down of Gli1 by siRNA interference reduced the viability of glioma cells as well as suppressed cell metastasis. Also, the inhibitory effects of cell survival by silenced Gli1 were abrogated by AQP1 overexpression. In summary, glioma cell survival is a regulatory process and can be mediated by Gli1-AQP1 pathway.