• IMMUNE NETWORK
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• v.2 no.3
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• pp.125-132
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• 2002

In the past, bioinformatics was often regarded as a difficult and rather remote field, practiced only by computer scientists and not a practical tool available to biologists. However, the various on-going genome projects have had a serious impact on biological sciences in various ways and now there is little doubt that bioinformatics is an essential part of the research environment, with a wealth of biological information to analyze and predict. Fully sequenced genomes made us to have additional insights into the functional properties of the encoded proteins and made it possible to develop new tools and schemes for functional biology on a proteomic scale. Among those are the yeast two-hybrid system, mass spectrometry and microarray: the technology of choice to detect protein-protein interactions. These functional insights emerge as networks of interacting proteins, also known as "pathway informatics" or "interactomics". Without exception it is no longer possible to make advances in the signaling/regulatory pathway studies without integrating information technologies with experimental technologies. In this paper, we will introduce the databases of protein interaction worldwide and discuss several challenging issues regarding the actual implementation of databases.

• BMB Reports
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• v.34 no.5
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• pp.452-456
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• 2001

Surface plasmon resonance has been used for a biospecific interaction analysis between two macromolecules in real time. Determination of an antibody that is capable of specifically interacting with the native form of antigen is very useful for many biological and medical applications. Twenty monoclonal antibodies against the $\alpha$ subunit of E. coli DNA polymerase III were screened for specifically recognizing the native form of protein using surface plasmon resonance. Only four monoclonal antibodies among them specifically recognized the native $\alpha$ protein, although all of the antibodies were able to specifically interact with the denatured $\alpha$ subunit. These antibodies failed to interfere with the interaction between the $\tau$ and $\alpha$ subunits that were required for dimerization of the two polymerases at the DNA replication fork. This real-time analysis using surface plasmon resonance provides an easy method to screen antibodies that are capable of binding to the native form of the antigen molecule and determine the biological interaction between the two molecules.

• Proceedings of the Korean Biophysical Society Conference
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• 2001.06a
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• pp.21-21
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• 2001

PDZ domains are molecular-recognition elements that mediate protein-protein interactions. The PDZ domain was discovered originally as a common motif present in three structurally related proteins： PSD-95 (postsynaptic density protein), Dlg (discs-large protein) and ZQ-1 (zonula occludens-1). The PDZ domain is globular domain, containing about 80-100 amino acids, and a conserved motif with two alpha helices and six beta strands. Most of them bind selectively to the C-termini of the interacting proteins at the complexes of signaling molecules and membrane associated receptors.(omitted)

• Proceedings of the Korea Information Processing Society Conference
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• 2011.11a
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• pp.1115-1118
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• 2011

단백질 사이의 상호작용 네트워크(PPI network: Protein-Protein Interaction network)를 이용하여 단백질 기능을 예측 하는 것은 단백질 기능 예측 기법들 중에서 중요한 작용을 한다. 하지만 PPI를 이용한 단백질 기능 예측은 기능의 복잡도와 다양성으로 인해 제한적인 결과를 나타내 왔다. 따라서 본 논문에서는 기존의 연구들 보다 높은 정확도로 단백질 기능을 예측하기 위해 기능 예측을 하려는 단백질과 상호작용 하는 단백질들에 그래프 마이닝 기법을 적용하여 빈발 2-노드 상호작용 패턴을 찾고, 그 패턴을 이용하여 단백질 기능을 예측하는 접근법을 제안하였다. 실험데이터로 DIP(Database of Interacting Proteins)에서 제공하는 단백질 상호작용 데이터를 사용하였으며, 다른 기존의 단백질 기능 예측 기법들보다 높은 정확도를 보여주었다.

• Journal of Microbiology and Biotechnology
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• v.12 no.6
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• pp.943-949
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• 2002

It has been proposed that chitin synthase 3 (CHS3)-nediated chitin synthesis during the vegetative cell cycle is regulated by chitin synthase 4 (CHS4) of Saccharomyces cerevisiae. To investigate direct protein-protein interaction between the coding products of these two genes, a domain of Chs3p that is responsible for interaction with Chs4p was identified, using the yeast two-hybrid system. This domain of 54 amino acids, termed MIRC3-4 (Maximum Interacting Region of Chs3p with Chs4p), is well conserved among CHS3 homologs of various fungi. Some mutations in MIRC3-4 resulted in a decrease in the enzymatic activity and chitin contents. Chs3p carrying those mutations exhibited weak interactions with Chs4p, when assayed by the yeast two-hybrid system. Surprisingly, all the mutants were sensitive to Calcofluor regardless of changes in enzymatic activities or chitin contents. This report deals with a core region in MIRC3-4 that affects the interaction with Chs4p.

• Molecules and Cells
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• v.21 no.3
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• pp.330-336
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• 2006

Since its identification in 1989, hepatitis C virus has been the subject of extensive research. The biology of the virus and the development of antiviral drugs are closely related. The RNA polymerase activity of nonstructural protein 5B was first demonstrated in 1996. NS5B is believed to localize to the perinuclear region, forming a replicase complex with other viral proteins. It has a typical polymerase structure with thumb, palm, and finger domains encircling the active site. A de novo replication initiation mechanism has been suggested. To date, many small molecule inhibitors are known including nucleoside analogues, non-nucleoside analogues, and pyrophosphate mimics. NS5B interacts with other viral proteins such as core, NS3, 4A, 4B, and 5A. The helicase activity of NS3 seems necessary for RNA strand unwinding during replication, with other nonstructural proteins performing modulatory roles. Cellular proteins interacting with NS5B include VAMP-associated proteins, heIF4AII, hPLIC1, nucleolin, PRK2, ${\alpha}$-actinin, and p68 helicase. The interactions of NS5B with these proteins might play roles in cellular trafficking, signal transduction, and RNA polymerization, as well as the regulation of replication/translation processes.

• BMB Reports
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• v.44 no.7
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• pp.490-495
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• 2011

Transcription factor AP-$2{\alpha}$ involves in the process of mammalian embryonic development and tumorigenesis. Many studies have shown that AP-$2{\alpha}$ functions in association with other interacting proteins. In a two-hybrid screening, the regulatory subunit ${\beta}$ of protein casein kinase 2 ($CK2{\beta}$) was identified as an interacting protein of AP-$2{\alpha}$; we confirmed this interaction using in-vitro GST pull-down and in-vivo co-immunoprecipitation assays; in an endogenous co-immunoprecipitation experiment, we further found the catalytic subunit ${\alpha}$ of protein casein kinase 2 ($CK2{\alpha}$) also exists in the complex. Phosphorylation analysis revealed that AP-$2{\alpha}$ was phosphorylated by CK2 kinase majorly at the site of Ser429, and such phosphorylation could be blocked by CK2 specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) in a dose-dependent manner. Luciferase assays demonstrated that both $CK2{\alpha}$ and $CK2{\beta}$ enhanced the transcription activity of AP-$2{\alpha}$; moreover, $CK2{\beta}$ increased the stability of AP-$2{\alpha}$. Our data suggest a novel cellular function of CK-2 as a transcriptional co-activator of AP-$2{\alpha}$.

• BMB Reports
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• v.43 no.5
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• pp.325-329
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• 2010

Protein kinase CKII (CKII), a heterotetramer composed of two catalytic ($\alpha$ or $\alpha$') subunits and two regulatory ($\beta$) subunits, plays a critical role in cell proliferation and anti-apoptosis. Recently, capsaicin was shown to trigger apoptosis. Therefore, we examined the effect of capsaicin on CKII activity. Although capsaicin induced apoptotic death in HeLa cells, CKII activity was increased in the cytosolic fraction of HeLa cells after treatment. Capsaicin did not change the expression of the $CKII{\alpha}$ and $CKII{\beta}$ proteins. Capsaicin stimulated the catalytic activity of recombinant CKII tetramer, but not the $CKII{\alpha}$ subunit. Moreover, capsaicin enhanced the autophosphorylation of $CKII{\alpha}$ and $CKII{\beta}$. Taken together, our data suggest that capsaicin stimulates the phosphotransferase activity of CKII holoenzyme by interacting with the $CKII{\beta}$ subunit.

• Development and Reproduction
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• v.26 no.3
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• pp.117-126
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• 2022

Bromodomain-containing protein 7 (BRD7) participates in many cellular processes and embryo development. BRD7 is down-regulated in various cancers and evidence of its tumor suppressor function has been accumulating. Here, we identified transforming stimulated clone 22 (TSC-22) as a novel BRD7 interacting protein and show its novel function as a positive regulator of BRD7. We found that TSC-22 expression potentiated the inactivation of the extracellular signal-regulate kinase (ERK) pathway by BRD7. Our data establishes TSC-22 as a modulator of BRD7 and unravels the molecular mechanisms that drive the synergistic tumor-suppressing effects of TSC-22 and BRD7. Our findings may open new avenues for developing novel molecular therapies for tumors exhibiting down-regulated BRD7 and/or TSC-22.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2953-2958
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• 2015

Although associations between thioredoxin interacting protein (TXNIP) and cancers have been recognized, the effects of TXNIP on non-small cell lung cancer (NSCLC) prognosis remained to be determined in detail. In addition, while hypoxia is a key characteristic of tumor cell growth microenvironment, the effect of hypoxia on TXNIP expression is controversial. In this study, formaldehyde fixed and paraffin embedded (FFPE) samples of 70 NSCLC patients who underwent resection between January 2010 and December 2011 were obtained. Evaluation of TXNIP and hypoxia inducible factor-$1{\alpha}$ ($HIF-1{\alpha}$) protein expression in FFPE samples was made by immunohistochemistry. By Kaplan-Meier method, patients with high TXNIP expression demonstrated a significantly shorter progression free survival (PFS) compared with those with low TXNIP expression (18.0 months, 95%CI: 11.7, 24.3 versus 23.0 months, 95%CI: 17.6, 28.4, P=0.02). High TXNIP expression level was also identified as an independent prognostic factor by Cox regression analysis (adjusted hazard ratio: 2.46; 95%CI: 1.08, 5.56; P=0.03). Furthermore, TXNIP expression was found to be significantly correlated with $HIF-1{\alpha}$ expression (Spearman correlation=0.67, P=0.000). To further confirm correlations, we established a tumor cell hypoxic culture model. Expression of TXNIP was up-regulated in all three NSCLC cell lines (A549, SPC-A1, and H1299) under hypoxic conditions. This study suggests that hypoxia induces increased TXNIP expression in NSCLC and high TXNIP expression could be a poor prognostic marker.