Article
Biochemistry & Molecular Biology
Eleni Petsouki, Sylvia Ender, Shara Natalia Sosa Cabrera, Elke H. Heiss
Summary: Nrf2 is a transcription factor that enhances cells' resilience against stress. It has been found that AMPK, a kinase that regulates cellular energy balance, has a potential cooperativity with Nrf2. Our study shows that AMPK-dependent phosphorylation sites in Nrf2 can influence its degradation and gene expression. This research is important for understanding the regulation of Nrf2 by AMPK.
Review
Cell Biology
Fumiyo Ikeda
Summary: Ubiquitin modifies diverse substrates through various conjugation types, regulating a wide range of biological functions. While the C-terminus of ubiquitin traditionally forms isopeptide or peptide bonds with protein substrates, recent studies have revealed that it can also form atypical oxyester bonds, targeting both proteinaceous and nonproteinaceous substrates such as sugars and lipids. The understanding of how nonprotein ubiquitination affects substrate and cellular functions is still incomplete. This review discusses recent discoveries in ubiquitination and its potential impacts on biology.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Felix Kraus, Ellen A. Goodall, Ian R. Smith, Yizhi Jiang, Julia C. Paoli, Frank Adolf, Jiuchun Zhang, Joao A. Paulo, Brenda A. Schulman, J. Wade Harper
Summary: Protein kinase PINK1 and ubiquitin ligase Parkin promote removal of damaged mitochondria through a feed-forward mechanism involving ubiquitin phosphorylation, Parkin activation, and ubiquitylation of mitochondrial outer membrane proteins. However, the involvement of FBXO7 in Parkin-dependent mitophagy is not supported by the findings of this study. FBXO7(-/-) cells showed no defects in various aspects of mitophagy, suggesting that additional studies are needed to understand how FBXO7 mutations contribute to Parkinsonian-pyramidal syndrome.
Article
Biochemistry & Molecular Biology
Jorg Schweiggert, Gregor Habeck, Sandra Hess, Felix Mikus, Roman Beloshistov, Klaus Meese, Shoji Hata, Klaus-Peter Knobeloch, Frauke Melchior
Summary: The ubiquitin E3 ligase SCFFbxw5 targets MCAK for proteasomal degradation during G(2), which promotes ciliogenesis starting in the preceding cell cycle phase. Loss of Fbxw5 results in increased MCAK levels at basal bodies and impairs ciliogenesis in the following G(1)/G(0).
Article
Biochemistry & Molecular Biology
Weaam Mohamed, Sophia L. Park, Julius Rabl, Alexander Leitner, Daniel Boehringer, Matthias Peter
Summary: The human GID (hGID) complex utilizes two distinct modules, WDR26 and GID4, for substrate recruitment and ubiquitination. GID4 functions as an adaptor for some substrates while WDR26 and Gid7 utilize different binding sites. The study also reveals the regulation of GID4 substrate binding and ligase activity by ARMC8 alpha.
Article
Chemistry, Medicinal
Serah W. Kimani, Julie Owen, Stuart R. Green, Fengling Li, Yanjun Li, Aiping Dong, Peter J. Brown, Suzanne Ackloo, David Kuter, Cindy Yang, Miranda MacAskill, Stephen Scott MacKinnon, Cheryl H. Arrowsmith, Matthieu Schapira, Vijay Shahani, Levon Halabelian
Summary: DCAF1 serves as a subunit for RING-type CRL4(DCAF1) and HECT family EDVPDCAF1 E3 ubiquitin ligases in substrate recruitment. The WDR domain of DCAF1 acts as a binding platform for substrate proteins and is targeted by HIV and SIV lentiviral adaptors. This study used a proteome-scale drug-target interaction prediction model to identify ligands for the DCAF1 WDR domain through biophysical screening and X-ray crystallography, confirming the selective binding of a predicted ligand. The findings demonstrate the successful application of artificial intelligence-enabled virtual screening methods in the absence of previously known ligands.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemical Research Methods
Zeliha Yalcin, Danielle Koot, Karel Bezstarosti, Daniel Salas-Lloret, Onno B. Bleijerveld, Vera Boersma, Mattia Falcone, Roman Gonzalez-Prieto, Maarten Altelaar, Jeroen A. A. Demmers, Jacqueline J. L. Jacobs
Summary: Ubiquitination plays a crucial role in cellular processes, but dysregulation of ubiquitin machinery enzymes can lead to pathogenesis. Defining in vivo substrates of individual ubiquitin-conjugating enzymes is challenging. In this study, we used proteomics methods to identify in vivo targets of UBE2D3, an E2 enzyme with unclear roles. UBE2D3 depletion affected the global proteome and the ubiquitinome, especially molecular pathways related to mRNA translation. Our findings show that UBE2D3 is involved in ribosome-associated protein quality control and autophagic protein quality control.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Biochemistry & Molecular Biology
Rebeca Ibarra, Heather R. Borror, Bryce Hart, Richard G. Gardner, Gary Kleiger
Summary: The yeast PQC ubiquitin ligase San1 contains multiple substrate binding sites along its polypeptide chain, showing specificity for unique misfolded proteins and enabling the formation of high affinity ubiquitin ligase-substrate complexes.
Article
Multidisciplinary Sciences
Saki Ichikawa, Hope A. Flaxman, Wenqing Xu, Nandini Vallavoju, Hannah C. Lloyd, Binyou Wang, Dacheng Shen, Matthew R. Pratt, Christina M. Woo
Summary: This study identifies C-terminal cyclic imides as physiological degrons for the ubiquitin E3 ligase substrate adapter cereblon (CRBN). The addition of these degrons induces CRBN-dependent ubiquitination and degradation of proteins. This discovery has significant implications for understanding the physiological and therapeutic engagement of CRBN.
Review
Cell Biology
Emma Rusilowicz-Jones, Ailbhe J. Brazel, Francesca Frigenti, Sylvie Urbe, Michael J. Clague
Summary: This article presents the comprehensive inventory and distribution of components in the ubiquitin system, focusing on their organization within different cellular compartments. It discusses the diverse cast of resident enzymes in the endoplasmic reticulum and endosomal compartments, as well as the more restricted palette in the Golgi and mitochondria.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Sachiho Taniguchi, Yuji Ono, Yukako Doi, Shogo Taniguchi, Yuta Matsuura, Ayuka Iwasaki, Noriaki Hirata, Ryosuke Fukuda, Keitaro Inoue, Miho Yamaguchi, Anju Tashiro, Daichi Egami, Shunsuke Aoki, Yasumitsu Kondoh, Kaori Honda, Hiroyuki Osada, Hiroyuki Kumeta, Tomohide Saio, Tsukasa Okiyoneda
Summary: RFFL is a highly expressed apoptotic inhibitor in cancers, and its inhibition suppresses cancer cell growth and enhances chemotherapy sensitivity. It has been discovered that α-tocopherol succinate (alpha TOS) can act as a ligand for RFFL, inhibiting the RFFL-substrate interaction and increasing the cell surface expression of CFTR channel, which may have therapeutic potential for both cancer and cystic fibrosis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Uwe Schulte, Fabian den Brave, Alexander Haupt, Arushi Gupta, Jiyao Song, Catrin S. S. Mueller, Jeannine Engelke, Swadha Mishra, Christoph Martensson, Lars Ellenrieder, Chantal Priesnitz, Sebastian P. P. Straub, Kim Nguyen Doan, Bogusz Kulawiak, Wolfgang Bildl, Heike Rampelt, Nils Wiedemann, Nikolaus Pfanner, Bernd Fakler, Thomas Becker
Summary: This study presents a quantitative mapping of mitochondrial protein assemblies using high-resolution complexome profiling. The results reveal the complex organization of mitochondrial protein assemblies involved in various cellular processes. It also identifies quality-control factors and elucidates a constitutive pathway for preprotein removal.
Editorial Material
Biochemistry & Molecular Biology
Benjamin Stieglitz
Summary: In this study, a multidisciplinary approach was used to investigate the enzymatic activity of RBR ligases, revealing an unexpected substrate binding site.
Article
Oncology
Feiyang Ji, Menghao Zhou, Zeyu Sun, Zhengyi Jiang, Huihui Zhu, Zhongyang Xie, Xiaoxi Ouyang, Lingjian Zhang, Lanjuan Li
Summary: The study revealed an increase in ubiquitinated sites with shorter chains during the progression of HCC metastasis, and high expression of E3 ubiquitin-protein ligase SYVN1 was found to be associated with tumor metastasis.
CANCER COMMUNICATIONS
(2021)
Article
Immunology
Wenbing Zhi, Xia Du, Ye Li, Chunliu Wang, Tingting Sun, Shiyu Zong, Qiqi Liu, Kai Hu, Yang Liu, Hong Zhang
Summary: The research shows that SPC has a therapeutic effect on asthma, reducing inflammation and pathological damage by targeting multiple key points. Proteomic and molecular docking screening results indicate that SPC acts on a variety of critical targets, making it a potential drug for treating asthma.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Yao-Cheng Li, Nikki K. Lytle, Seth T. Gammon, Luke Wang, Tikvah K. Hayes, Margie N. Sutton, Robert C. Bast, Channing J. Der, David Piwnica-Worms, Frank McCormick, Geoffrey M. Wahl
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Integrative & Complementary Medicine
Hyo In Kim, Sol Ji Lee, Yu-Jeong Choi, Min Jeong Kim, Tai Young Kim, Seong-Gyu Ko
Summary: This study found that quercetin can induce apoptosis in GBM cells by inhibiting the Axl/IL-6/STAT3 signaling pathway, suggesting its potential as an anticancer agent.
AMERICAN JOURNAL OF CHINESE MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Jennifer E. Klomp, Jeff A. Klomp, Channing J. Der
Summary: The RAF-MEK-ERK mitogen-activated protein kinase (MAPK) cascade is extensively studied and targeted by pharmaceutical industry. The ERK-MAPK cascade, initially thought to be a linear pathway, is now understood as a complex network with dynamic signaling inputs and outputs. Despite advances in understanding, the adaptability of cancer cells to inhibition of key nodes reveals a complexity that is not fully understood.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Oncology
Sol Ji Lee, Yu-Jeong Choi, Hyo In Kim, Hyo Eun Moon, Sun Ha Paek, Tai Young Kim, Seong-Gyu Ko
Summary: The study identified Platycodon grandiflorus and its component platycodin D as inhibitors of autophagy in glioblastoma multiforme cells. The mechanism involves preventing lysosomal degradation and disrupting cholesterol trafficking, leading to cell death. These findings suggest potential for platycodin D as an anti-GBM drug.
MOLECULAR ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Minwoo Wendy Jang, Doo-Yi Oh, Eunyoung Yi, Xuezhong Liu, Jie Ling, Nayoung Kim, Kushal Sharma, Tai Young Kim, Seungmin Lee, Ah-Reum Kim, Min Young Kim, Min-A Kim, Mingyu Lee, Jin-Hee Han, Jae Joon Han, Hye-Rim Park, Bong Jik Kim, Sang-Yeon Lee, Dong Ho Woo, Jayoung Oh, Soo-Jin Oh, Tingting Du, Ja-Won Koo, Seung-Ha Oh, Hyun-Woo Shin, Moon-Woo Seong, Kyu-Yup Lee, Un-Kyung Kim, Jung Bum Shin, Shushan Sang, Xinzhang Cai, Lingyun Mei, Chufeng He, Susan H. Blanton, Zheng-Yi Chen, Hongsheng Chen, Xianlin Liu, Aida Nourbakhsh, Zaohua Huang, Kwon-Woo Kang, Woong-Yang Park, Yong Feng, C. Justin Lee, Byung Yoon Choi
Summary: The study identified a deafness gene TMEM43 associated with progressive deafness, mainly expressed in cochlear glia-like supporting cells. Cochlear implantation was performed on patients with ANSD caused by TMEM43 gene mutation, successfully restoring speech discrimination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Wen-Hsuan Chang, Thuy-Tien Thi Nguyen, Chia-Hsin Hsu, Kirsten L. Bryant, Hong Jin Kim, Haoqiang Ying, Jon W. Erickson, Channing J. Der, Richard A. Cerione, Marc A. Antonyak
Summary: KRAS mutations lead to the production of exosomes enriched with the cell survival protein Survivin, which enhance cancer cell survival and resistance to chemotherapy drugs. Targeting Survivin within these exosomes could potentially serve as a therapeutic strategy for KRAS-dependent cancers.
Article
Multidisciplinary Sciences
Jason W. Miklas, Shiri Levy, Peter Hofsteen, Diego Ic Mex, Elisa Clark, Jeanot Muster, Aaron M. Robitaille, Gargi Sivaram, Lauren Abell, Jamie M. Goodson, Inez Pranoto, Anup Madan, Michael T. Chin, Rong Tian, Charles E. Murry, Randall T. Moon, Yuliang Wang, Hannele Ruohola-Baker
Summary: The ability of zebrafish and neonatal mouse myocardial cells to regenerate the heart through dedifferentiation and proliferation is explored. The study demonstrates a unique metabolic state and mitochondrial changes that contribute to this regenerative capability.
Article
Biochemistry & Molecular Biology
Megan J. Agajanian, Frances M. Potjewyd, Brittany M. Bowman, Smaranda Solomon, Kyle M. LaPak, Dhaval P. Bhatt, Jeffery L. Smith, Dennis Goldfarb, Alison D. Axtman, Michael B. Major
Summary: This study reveals that CSNK1 gamma 3 activates the beta-catenin-dependent WNT signaling pathway and induces phosphorylation of low-density lipoprotein receptor-related protein 6. While the expression of CSNK1 gamma 3 can drive WNT pathway activity, potential functional redundancy within the family necessitates the loss of all three family members to suppress WNT signaling pathway.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Microbiology
Tai Young Kim, Sangeun Jeon, Meehyun Ko, Young Eun Du, So-Ri Son, Dae Sik Jang, Seungtaek Kim, C. Justin Lee
Summary: The study found that Codonopsis lanceolate extract and its active compound lancemaside A have potent inhibitory activity against SARS-CoV-2 infection. The inhibitory effect is achieved by altering membrane cholesterol and blocking membrane fusion between the virus and host cells. Furthermore, lancemaside A can also block the entry pathways of different SARS-CoV-2 variants and prevent the formation of multinucleated syncytia caused by viral spike protein-mediated membrane fusion.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Editorial Material
Oncology
Adrienne D. Cox, Jenny P. -Y. Ting, Channing J. Der
Summary: Hattori and colleagues developed drug-peptide conjugates using targeted small-molecule covalent inhibitors to generate cancer neoantigens, inducing an immune response against oncogene-mutant cancer cells. This immunotherapy strategy shows potential in overcoming treatment-induced resistance commonly observed in small molecule-based targeted anticancer drugs.
Article
Biochemistry & Molecular Biology
Yu-Jeong Choi, Youn Kyung Choi, Seong-Gyu Ko, Chunhoo Cheon, Tai Young Kim
Summary: Costunolide (CTL) induces apoptosis by increasing reactive oxygen species (ROS) generation in cancer cells. It has a stronger cytotoxic effect on SK-BR-3 cells compared to MCF-7 cells. This difference is due to the activation of mitochondrial-dependent intrinsic apoptosis pathway in SK-BR-3 cells and PINK1/Parkin-dependent mitophagy pathway in MCF-7 cells in response to CTL treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mingu Gordon Park, Ah-reum Han, Su Yeon Kim, Tai Young Kim, Ho Min Kim, C. Justin Lee
Summary: This study introduces an optimized method for overexpressing 6xHis-tagged human GABA-T in human cells and establishing an activity assay, providing insights into the sensitivity differences between human and bacterial GABA-T to inhibitory compounds.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Benjamin Cyge, Vera Voronina, Mohammed Hoque, Eunice N. Kim, Jason Hall, Jennifer M. Bailey-Lundberg, Gregory J. Pazour, Howard C. Crawford, Randall T. Moon, Feng-Qian Li, Ken-Ichi Takemaru
Summary: Primary cilia act as sensory organelles regulating diverse biological processes, and dysfunction is associated with genetic disorders known as ciliopathies. Cby1 knockout mice develop severe exocrine pancreatic atrophy with dilated ducts during early postnatal development, leading to cell death and progressive pancreatic degeneration.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Tai Young Kim, Sangeun Jeon, Youngho Jang, Lizaveta Gotina, Joungha Won, Yeon Ha Ju, Sunpil Kim, Minwoo Wendy Jang, Woojin Won, Mingu Gordon Park, Ae Nim Pae, Sunkyu Han, Seungtaek Kim, C. Justin Lee
Summary: The study shows that platycodin D (PD) effectively blocks SARS-CoV-2 infection routes by preventing membrane fusion through cholesterol redistribution, suggesting a potent natural product for preventing or treating COVID-19.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Jiongjia Cheng, Masanao Tsuda, Karl Okolotowicz, Mary Dwyer, Paul J. Bushway, Alexandre R. Colas, Joseph J. Lancman, Dennis Schade, Isaac Perea-Gil, Arne A. N. Bruyneel, Jaechol Lee, Nirmal Vadgama, Justine Quach, Wesley L. McKeithan, Travis L. Biechele, Joseph C. Wu, Randall T. Moon, P. Duc Si Dong, Ioannis Karakikes, John R. Cashman, Mark Mercola
Summary: The study revealed a molecular cascade linking stress signaling to the regulation of TCF/LEF transcriptional activity, providing insights into how stress can control cell shape and renewal. These findings have implications for understanding tissue morphogenesis and anticancer therapeutics.
CELL CHEMICAL BIOLOGY
(2021)