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KAIST research team develops clathrin assembly for targeted protein delivery to cancer cells
In order to effectively treat cancer without additional side effects, we need a way to deliver drugs specifically to tumor cells. Protein assemblies have been widely used for drug delivery in the field of cancer treatment, but to use them for drug delivery they must first be functionalized, meaning they must be bound to the protein that recognizes the target tumor cell and deliver a drug that kills it. However, the functionalization process of protein assemblies is very complex, inefficient, and limited to small-sized chemical drugs, which limits their real-life applicability. On March 14, a KAIST research team led by Professor Hak-Sung Kim from the KAIST Department of Biological Sciences reported the development of a clathrin assembly that can specifically deliver drugs to cancer cells. Clathrin assemblies transport materials efficiently through endocytosis in living organisms. They are formed by the self-assembly of triskelion units, which are composed of three heavy chains bonded with three light chains. Inspired by this mechanism, the research team designed a clathrin chain to facilitate the functionalization of tumor cell recognition proteins and toxin proteins in order to deliver drugs specifically to tumor cells. From this, the team created a new type of clathrin assembly. Figure 1. (Upper) Schematic diagram of the development of a new clathrin assembly that simultaneously functionalizes two types of proteins (cancer cell recognition protein and toxin protein) on heavy and light chains of clathrin in a one-pot reaction (bottom, left) Electron microscopy image of clathrin assembly: formation of an assembly with a diameter of about 28 nanometers (bottom, right) Cancer cell killing effect of CLA: CLA functionalized with epidermal growth factor receptor (EGFR) recognition protein and toxin protein kills only the cancer cells that overexpress EGFR. The newly developed clathrin assembly requires a one-pot reaction, meaning both the toxin and tumor-recognition proteins can be functionalized simultaneously and show high efficiency. As a result, this technique is expected to be used in a wide variety of applications in the fields of biology and medicine including drug delivery, vaccine development, and diagnosing illnesses. In this research, an epidermal growth factor receptor (EGFR), a common tumor marker, was used as the recognition protein, allowing drug delivery only to tumor cells. The clathrin assemblies that were functionalized to recognize EGFR showed a bonding strength 900-times stronger than it normally would due to the avidity effect. Based on this finding, the research team confirmed that treatment with toxin-functionalized clathrin assembly led to effective cell death for tumor cells, while it showed no such effect on healthy cells. This research by Dr. Hong-Sik Kim and his colleagues was published in Small volume 19, issue 8 on February 22 under the title, "Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery", and it was selected as the cover paper. Figure 2. Cover Paper: This study was published in the international journal 'Small' on February 22nd, Volume 19, No. 8, and was selected as the cover paper. First author Dr. Hong-Sik Kim said, “Clathrin is difficult to functionalize, and since it is extracted from mammals, realistic applications have been limited.” He added, “But the new clathrin assembly we designed for this research can be functionalized with two different types of proteins through a single-step reaction, and can be produced from E. coli, meaning it can become an applicable protein assembly technology for a wide range of biomedical fields.” This research was funded by the Global Ph.D. Fellowship and the Mid-career Researcher Grant of the National Research Foundation.
A Genetic Change for Achieving a Long and Healthy Life
Researchers identified a single amino acid change in the tumor suppressor protein in PTEN that extends healthy periods while maintaining longevity Living a long, healthy life is everyone’s wish, but it is not an easy one to achieve. Many aging studies are developing strategies to increase health spans, the period of life spent with good health, without chronic diseases and disabilities. Researchers at KAIST presented new insights for improving the health span by just regulating the activity of a protein. A research group under Professor Seung-Jae V. Lee from the Department of Biological Sciences identified a single amino acid change in the tumor suppressor protein phosphatase and tensin homolog (PTEN) that dramatically extends healthy periods while maintaining longevity. This study highlights the importance of the well-conserved tumor suppressor protein PTEN in health span regulation, which can be targeted to develop therapies for promoting healthy longevity in humans. The research was published in Nature Communications on September 24, 2021. Insulin and insulin-like growth factor-1 (IGF-1) signaling (IIS) is one of the evolutionarily conserved aging-modulatory pathways present in life forms ranging from tiny roundworms to humans. The proper reduction of IIS leads to longevity in animals but often causes defects in multiple health parameters including impaired motility, reproduction, and growth. The research team found that a specific amino acid change in the PTEN protein improves health status while retaining the longevity conferred by reduced IIS. They used the roundworm C. elegans, an excellent model animal that has been widely used for aging research, mainly because of its very short normal lifespan of about two to three weeks. The PTEN protein is a phosphatase that removes phosphate from lipids as well as proteins. Interestingly, the newly identified amino acid change delicately recalibrated the IIS by partially maintaining protein phosphatase activity while reducing lipid phosphatase activity. As a result, the amino acid change in the PTEN protein maintained the activity of the longevity-promoting transcription factor Forkhead Box O (FOXO) protein while restricting the detrimental upregulation of another transcription factor, NRF2, leading to long and healthy life in animals with reduced IIS. Professor Lee said, “Our study raises the exciting possibility of simultaneously promoting longevity and health in humans by slightly tweaking the activity of one protein, PTEN.” This work was supported by the MInistry of Science and ICT through the National Research Foundation of Korea. -Publication:Hae-Eun H. Park, Wooseon Hwang, Seokjin Ham, Eunah Kim, Ozlem Altintas, Sangsoon Park, Heehwa G. Son, Yujin Lee, Dongyeop Lee, Won Do Heo, and Seung-Jae V. Lee. 2021. “A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling,” Nature Communications, 12(1), 5631. (https://doi.org/10.1038/s41467-021-25920-w) -ProfileProfessor Seung-Jae V. LeeMolecular Genetics of Aging LaboratoryDepartment of Biological Sciences KAIST
The Dynamic Tracking of Tissue-Specific Secretory Proteins
Researchers develop a versatile and powerful tool for studying the spatiotemporal dynamics of secretory proteins, a valuable class of biomarkers and therapeutic targets Researchers have presented a method for profiling tissue-specific secretory proteins in live mice. This method is expected to be applicable to various tissues or disease models for investigating biomarkers or therapeutic targets involved in disease progression. This research was reported in Nature Communications on September 1. Secretory proteins released into the blood play essential roles in physiological systems. They are core mediators of interorgan communication, while serving as biomarkers and therapeutic targets. Previous studies have analyzed conditioned media from culture models to identify cell type-specific secretory proteins, but these models often fail to fully recapitulate the intricacies of multi-organ systems and thus do not sufficiently reflect biological realities. These limitations provided compelling motivation for the research team led by Jae Myoung Suh and his collaborators to develop techniques that could identify and resolve characteristics of tissue-specific secretory proteins along time and space dimensions. For addressing this gap in the current methodology, the research team utilized proximity-labeling enzymes such as TurboID to label secretory proteins in endoplasmic reticulum lumen using biotin. Thereafter, the biotin-labeled secretory proteins were readily enriched through streptavidin affinity purification and could be identified through mass spectrometry. To demonstrate its functionality in live mice, research team delivered TurboID to mouse livers via an adenovirus. After administering the biotin, only liver-derived secretory proteins were successfully detected in the plasma of the mice. Interestingly, the pattern of biotin-labeled proteins secreted from the liver was clearly distinctive from those of hepatocyte cell lines. First author Kwang-eun Kim from the Graduate School of Medical Science and Engineering explained, “The proteins secreted by the liver were significantly different from the results of cell culture models. This data shows the limitations of cell culture models for secretory protein study, and this technique can overcome those limitations. It can be further used to discover biomarkers and therapeutic targets that can more fully reflect the physiological state.” This work research was supported by the National Research Foundation of Korea, the KAIST Key Research Institutes Project (Interdisciplinary Research Group), and the Institute for Basic Science in Korea. -PublicationKwang-eun Kim, Isaac Park et al., “Dynamic tracking and identification of tissue-specific secretory proteins in the circulation of live mice,” Nature Communications on Sept.1, 2021(https://doi.org/10.1038/s41467-021-25546-y) -ProfileProfessor Jae Myoung Suh Integrated Lab of Metabolism, Obesity and Diabetes Researchhttps://imodkaist.wixsite.com/home Graduate School of Medical Science and Engineering College of Life Science and BioengineeringKAIST
X-ray Scattering Shines Light on Protein Folding
- Multiple forms of a non-functional, unfolded protein follow different pathways and timelines to reach its folded, functional state, a study reveals. - KAIST researchers have used an X-ray method to track how proteins fold, which could improve computer simulations of this process, with implications for understanding diseases and improving drug discovery. Their findings were reported in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 30. When proteins are translated from their DNA codes, they quickly transform from a non-functional, unfolded state into their folded, functional state. Problems in folding can lead to diseases like Alzheimer’s and Parkinson’s. “Protein folding is one of the most important biological processes, as it forms the functioning 3D protein structure,” explained the physical chemist Hyotcherl Ihee of the Department of Chemistry at KAIST. Dr. Tae Wu Kim, the lead author of this research from Ihee’s group, added, “Understanding the mechanisms of protein folding is important, and could pave the way for disease study and drug development.” Ihee’s team developed an approach using an X-ray scattering technique to uncover how the protein cytochrome c folds from its initial unfolded state. This protein is composed of a chain of 104 amino acids with an iron-containing heme molecule. It is often used for protein folding studies. The researchers placed the protein in a solution and shined ultraviolet light on it. This process provides electrons to cytochrome c, reducing the iron within it from the ferric to the ferrous form, which initiates folding. As this was happening, the researchers beamed X-rays at very short intervals onto the sample. The X-rays scattered off all the atomic pairs in the sample and a detector continuously recorded the X-ray scattering patterns. The X-ray scattering patterns provided direct information regarding the 3D protein structure and the changes made in these patterns over time showed real-time motion of the protein during the folding process. The team found cytochrome c proteins initially exist in a wide variety of unfolded states. Once the folding process is triggered, they stop by a group of intermediates within 31.6 microseconds, and then those intermediates follow different pathways with different folding times to reach an energetically stable folded state. “We don’t know if this diversity in folding paths can be generalized to other proteins,” Ihee confessed. He continued, “However, we believe that our approach can be used to study other protein folding systems.” Ihee hopes this approach can improve the accuracy of models that simulate protein interactions by including information on their unstructured states. These simulations are important as they can help identify barriers to proper folding and predict a protein’s folded state given its amino acid sequence. Ultimately, the models could help clarify how some diseases develop and how drugs interact with various protein structures. Ihee’s group collaborated with Professor Young Min Rhee at the KAIST Department of Chemistry, and this work was supported by the National Research Foundation of Korea (NRF) and the Institute for Basic Science (IBS). Figure. The scientists found that non-functional unfolded forms of the protein cytochrome c follow different pathways and timelines to reach a stable functional folded state. Publications: Kim, T. W., et al. (2020) ‘Protein folding from heterogeneous unfolded state revealed by time-resolved X-ray solution scattering’. PNAS. Volume 117. Issue 26. Page 14996-15005. Available online at https://doi.org/10.1073/pnas.1913442117 Profile: Hyotcherl Ihee, Ph.D. Professor email@example.com http://time.kaist.ac.kr/ Ihee Laboratory Department of Chemistry KAIST https://www.kaist.ac.kr Daejeon 34141, Korea Profile: Young Min Rhee, Ph.D. Professor firstname.lastname@example.org http://singlet.kaist.ac.kr Rhee Research Group Department of Chemistry KAIST https://www.kaist.ac.kr Daejeon 34141, Korea (END)
Professor Hee-Sung Park Named Scientist of May
(Professor Hee-Sung Park) Professor Hee-Sung Park from the Department of Chemistry was named ‘Scientist of May’ sponsored by the Ministry of Science and ICT and the National Research Foundation of Korea. Professor Park was honored in recognition of his developing a tool to engineer designer proteins via diverse chemical modifications. This approach provides a novel platform for investigating numerous diseases such as cancer and dementia. His research focuses on the production of synthetic proteins and the generation of diverse protein functions as well as the designing and engineering of new translation machinery for genetic code expansion, and the application of synthetic biology techniques for basic cell biology and applied medical science. Post-translational modifications (PTMs) are constantly taking place during or after protein biosynthesis. PTMs play a vital role in expanding protein functional diversity and, as a result, critically affect numerous biological processes. Abnormal PTMs have been known to trigger various diseases including cancer and dementia. Therefore, this technology enables proteins to reproduce with specific modifications at selected residues and will significantly help establish experimental strategies to investigate fundamental biological mechanisms including the development of targeted cancer therapies. Professor Park also received 10 million KRW in prize money.
Dr. Ryu of KAIST Receives the S-Oil Outstanding Paper Award
Dr. Je-Kyung Ryu of KAIST’s Department of Physics has been awarded the S-Oil Outstanding Paper Award for his doctoral dissertation’s originality and applicability. Professor Tae-Young Yoon of Physics is his doctoral advisor. The award ceremony took place on November 25, 2015 at the Press Center in Seoul. This S-Oil Outstanding Paper Award, jointly sponsored by the Korean Academy of Science and Technology (KAST) and the Scholastic University Presidential Association, was established to foster young talented scientists in basic science and to advance the field. The award is given every other year for each of the fields of physics, chemistry, mathematics, biology, and earth sciences. With the award, Dr. Ryu received a research grant of USD 8,600. He discovered, for the first time in the world, how NSF (N-ethylmaleimide-sensitive factor), a protein involved in a vesicular transport in cellular activities, disassembles a SNARE (soluble NSF attachment protein receptor) complex, using a unimolecular biophysics method. Unlike the existing studies, he proposed a model in which NSF disassembles SNARE complexes at one step, and as a result, provided evidence of how the SNARE complex influenced the fusion of biological membranes. His research was published in the scientific journal Science issued on March 27, 2015. The title of the paper is “Spring-loaded Unraveling of a Single SNARE Complex by NSF in One Round of ATP Turnover.”
Mapping the Folding Process of a Single Membrane Protein
KAIST and UCLA scientists were able to observe an individual membrane protein fold and unfold by pulling and releasing magnetically trapped protein molecules. Proteins are huge molecules containing hundreds to thousands of atoms that adopt a unique three dimensional structure, placing chemical groups in just the right place to catalyze reactions or build cellular structures. How all those atoms manage to find the right location - the so-called folding problem - has fascinated molecular biologists since the first structures were seen in the 1950s. Moreover, folding has important medical implications because most genetic defects cause protein misfolding. About a third of all proteins float around in the cell membrane where they ensure the right chemicals get in the cell in the right amounts. Membrane proteins also provide key information links between the cell and its environment. Indeed, most drugs target membrane proteins. Nevertheless, the folding of membrane proteins has been particularly difficult to study and has rarely been studied in natural environments, leaving the folding process for a large fraction of the protein universe still largely cloaked in mystery. In a recent issue of Nature Chemical Biology, published on October 19, 2015, a research team led by Tae-Young Yoon of the Department of Physics at the Korea Advanced Institute of Science and Technology (KAIST) and James U. Bowie of the Department of Chemistry and Biochemistry at the University of California, Los Angeles (UCLA), report a new method for manipulating the folding of membrane proteins in a membrane environment using a tool called a magnetic tweezer. Researchers first attach long DNA handles to the ends of the protein. One handle is attached to a glass surface and the other to a magnetic bead. Using a magnet, they can essentially grab the protein and pull on it, inducing it to unfold. By playing with the bead attached to the protein, they can force the protein to unfold or allow it to refold, and watch all this happening by 3D-tracking of the magnetic bead. With this novel strategy, they were able to quantitatively map the folding energy landscape, the folding kinetic rate, and folding intermediates of a membrane protein in a membrane environment for the first time. “I have been dreaming about this experiment for a decade. To see it work so well is really gratifying,” said Dr. Bowie. One of the major surprises in the study was that essentially all the atoms of the protein jump into the correct structure together. The researchers expected that the protein structure would come together in a more piecemeal fashion, with different parts of the structure forming separately, but that was not the case. It is possible that nature evolved such a smooth, highly cooperative folding process to prevent partially folded forms that could get into trouble in the crowded cell membrane. On the other hand, the cooperative folding seen here might not apply to other membrane proteins. “We need to look at more proteins. The technique developed here may allow us to do just that,” said Dr. Yoon. The single molecule mechanical manipulation technique could enable detailed folding studies of many other membrane proteins. A major barrier to the study of membrane proteins previously is that the proteins tend to stick together and get tangled up, as computer cords lying at your feet tend to do. With the tweezer technique used in this work, the protein cords are held apart from other cords so they can’t get knotted up. It is hoped that the new approach will open up an important part of the protein universe to scrutiny, including many proteins that become misfolded in disease states. The title of the research paper is “Mapping the energy landscape for second-stage folding of a single membrane protein” (DOI: 10.1038/nchembio.1939). Picture: Single-molecule magnetic tweezers that induce mechanical unfolding and refolding of a single membrane protein. Since the force applied is parallel to the biological lipid membrane, the unfolding and refolding processes occur within the membrane.
Professor Ki-Jun Jeong Wins the 2015 Dam Yeun Academic Award
The 11th Dam Yeun Academic Award presented by the Korean Society for Biotechnology and Bioengineering (KSBB) to a biologist under 45 years old went to Professor Ki-Jun Jeong of the Chemical and Biomolecular Engineering Department at KAIST. The award ceremony took place on October 13, 2015, at the annual conference of KSBB held at Songdo Convensia in Incheon City. Each year KSBB announces the recipient of the award based on the publications by researchers in the last five years at peer-reviewed international journals or KSBB Journal as well as the record of patent registration and technology transfers. Professor Jeong is recognized for his pioneering research in protein, antibody, cellular engineering, and protein displays and chips.
Professor Kwang-Hyun Cho Recognzied by "Scientist of the Month" Award
Professor Kwang-Hyun Cho of KAIST’s Department of Bio and Brain Engineering received the “Scientist of the Month” award in February 2015 from the Ministry of Science, ICT, and Future Planning of the Republic of Korea and the National Research Foundation of Korea. The award was in recognition of Professor Cho’s contribution to the advanced technique of controlling the death of cancer cells based on systems biology, a convergence research in information technology (IT) and biotechnology. Professor Cho has published around 140 articles in international journals, including 34 papers in renowned science journals such as Nature, Science, and Cell in the past three years. His work also includes systems biology textbooks and many entries in international academic encyclopaedia. His field, systems biology, is a new biological research paradigm that identifies and controls the fundamental principles of organisms on a systems level. A well-known tumour suppressor protein, p53, is known to suppress abnormal cell growth and promote apoptosis of can cells, and thus was a focus of research by many scientists, but its effect has been insignificant and brought many side effects. This was due to the complex function of p53 that controls various positive and negative feedbacks. Therefore, there was a limit to understanding the protein with the existing biological approach. However, Professor Cho found the kinetic change and function of p53 via a systems biology approach. By applying IT technology to complex biological networks, he also identified the response to stress and the survival and death signal transduction pathways of cardiomyocytes and developed new control methods for cancer cells. Professor Cho said, “This award served as a momentum to turn over a new leaf.” He added, “I hope convergence research such as my field will bring more innovative ideas on the boundaries of academia.”
Nanoparticle Cluster Manufacturing Technique Using DNA Binding Protein Developed
Professor Hak-Sung Kim of the Department of Biological Sciences at KAIST and Yiseul Ryu, a doctoral candidate, used the Zinc Finger protein that specifically binds to target DNA sequence to develop a new manufacturing technique for size-controllable magnetic Nanoparticle Clusters (NPCs). Their research results were published in Angewandte Chemie International Edition online on 25 November 2014. NPCs are structures consisting of magnetic nanoparticles, gold nanoparticles, and quantum dots, each of which are smaller than 100 nm (10-9m). NPCs have a distinctive property of collectivity not seen in single nanoparticles. Specifically NPCS differ in physical and optical properties such as Plasmon coupling absorbance, energy transfers between particles, electron transfers, and conductivity. Therefore, NPCs can be employed in biological and medical research as well as the development of nanoelectric and nanoplasmon devices. To make use of these novel properties, the size and the composition of the cluster must be exquisitely controlled. However, previous techniques relied on chemical binding which required complex steps, making it difficult to control the size and composition of NPCs. Professor Kim’s team used Zinc Finger, a DNA binding protein, to develop a NPCs manufacturing technique to create clusters of the desired size easily. The Zinc Finger protein contains a zinc ion and specifically recognizes DNA sequence upon binding, which allows the exquisite control of the size and the cluster composition. The technique is also bio-friendly. Professor Kim’s team created linear structure of different sizes of NPCs using Zinc Finger proteins and three DNA sequences of different lengths. The NPCs they produced confirmed their ability to control the size and structure of the cluster by using different DNA lengths. The NPCs showed tripled T2 relaxation rates compared to the existing MRI contrast media (Feridex) and effectively transported to targeted cells. The research findings show the potential use of NPCs in biological and medical fields such as MRI contrast media, fluorescence imaging, and drug transport. The research used the specific binding property of protein and DNA to develop a new method to create an inorganic nanoparticle’s supramolecular assembly. The technique can be used and applied extensively in other nanoparticles for future research in diagnosis, imaging, and drug and gene delivery. Figure 1. A Mimetic Diagram of NPCs Manufacturing Technique Using DNA Binding Protein Zinc Finger Figure 2. Transmission Electron Microscopy Images showing different sizes of NPCs depending on the length of the DNA
Binding Regulatory Mechanism of Protein Biomolecules Revealed
Professor Hak-Sung Kim A research team led by Professor Hak-Sung Kim of Biological Sciences, KAIST, and Dr. Mun-Hyeong Seo, KAIST, has revealed a regulatory mechanism that controls the binding affinity of protein’s biomolecules, which is crucial for the protein to recognize molecules and carry out functions within the body. The research results were published in the April 24th online edition of Nature Communications. The protein, represented by enzyme, antibody, or hormones, specifically recognizes a variety of biomolecules in all organisms and implements signaling or immune response to precisely adjust and maintain important biological processes. The protein binding affinity of biomolecules plays a crucial role in determining the duration of the bond between two molecules, and hence to determine and control the in-vivo function of proteins. The researchers have noted that, during the process of proteins’ recognizing biomolecules, the protein binding affinity of biomolecules is closely linked not only to the size of non-covalent interaction between two molecules, but also to the unique kinetic properties of proteins. To identify the basic mechanism that determines the protein binding affinity of biomolecules, Professor Kim and his research team have made mutation in the allosteric site of protein to create a variety of mutant proteins with the same chemical binding surface, but with the binding affinity vastly differing from 10 to 100 times. The allosteric site of the protein refers to a region which does not directly bind with biomolecules, but crucially influences the biomolecule recognition site. Using real-time analysis at the single-molecule level of unique kinetic properties of the produced mutant proteins, the researchers were able to identify that the protein binding affinity of biomolecules is directly associated with the protein’s specific kinetic characteristics, its structure opening rate. Also, by proving that unique characteristics of the protein can be changed at the allosteric site, instead of protein’s direct binding site with biomolecules, the researchers have demonstrated a new methodology of regulating the in-vivo function of proteins. The researchers expect that these results will contribute greatly to a deeper understanding of protein’s nature that governs various life phenomena and help evaluate the proof of interpreting protein binding affinity of biomolecules from the perspective of protein kinetics. Professor Kim said, “Until now, the protein binding affinity of biomolecules was determined by a direct interaction between two molecules. Our research has identified an important fact that the structure opening rate of proteins also plays a crucial role in determining their binding affinity.” [Picture] A correlation graph of opening rate (kopening) and binding affinity (kd) between protein’s stable, open state and its unstable, partially closed state.
Mechanism in regulation of cancer-related key enzyme, ATM, for DNA damage and repair revealed
Professor Kwang-Wook Choi A research team led by Professor Kwang-Wook Choi and Dr. Seong-Tae Hong from the Department of Biological Sciences at KAIST has successfully investigated the operational mechanism of the protein Ataxia Telangiectasia Mutated (ATM), an essential protein to the function of a crucial key enzyme that repairs the damaged DNA which stores biometric information. The results were published on December 19th Nature Communications online edition. All organisms, including humans, constantly strive to protect the information within their DNA from damages posed by a number of factors, such as carbonized materials in our daily food intake, radioactive materials such as radon emitting from the cement of buildings or ultraviolet of the sunlight, which could be a trigger for cancer. In order to keep the DNA information safe, the organisms are always carrying out complex and sophisticated DNA repair work, which involves the crucial DNA damage repair protein ATM. Consequently, a faulty ATM leads to higher risks of cancer. Until now, academia predicted that the Translationally Controlled Tumor Protein (TCTP) will play an important role in regulating the function of ATM. However, since most of main research regarding TCTP has only been conducted in cultured cells, it was unable to identify exactly what mechanisms TCTP employs to control ATM. The KAIST research team identified that TCTP can combine with ATM or increase the enzymatic activity of ATM. In addition, Drosophilia, one of the most widely used model organisms for molecular genetics, has been used to identify that TCTP and ATM play a very important role in repairing the DNA damaged by radiation. This information has allowed the researchers to establish TCTP’s essential function in maintaining the DNA information in cell cultures and even in higher organisms, and to provide specific and important clues to the regulation of ATM by TCTP. Professor Kwang-Wook Choi said, “Our research is a good example that basic research using Drosophilia can make important contributions to understanding the process of diseases, such as cancer, and to developing adequate treatment.” The research has been funded by the Ministry of Science, ICT and Future Planning, Republic of Korea, and the National Research Foundation of Korea. Figure 1. When the amount of TCTP protein is reduced, cells of the Drosophila's eye are abnormally deformed by radiation. Scale bars = 200mm Figure 2. When the amount of TCTP protein is reduced, the chromosomes of Drosophilia are easily broken by radiation. Scale bars = 10 mm. Figure 3. When gene expressions of TCTP and ATM are reduced, large defects occur in the normal development of the eye. (Left: normal Drosophilia's eye, right: development-deficient eye) Figure 4. ATM marks the position of the broken DNA, with TCTP helping to facilitate this reaction. DNA (blue line) within the cell nucleus is coiled around the histone protein (green cylinder). When DNA is broken, ATM protein attaches a phosphate group (P). Multiple DNA repair protein recognizes the phosphate as a signal that requires repair and gathers at the site.
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