Article
Biochemistry & Molecular Biology
Katarzyna Retzer, Jeanette Moulinier-Anzola, Rebecca Lugsteiner, Nataliia Konstantinova, Maximilian Schwihla, Barbara Korbei, Christian Luschnig
Summary: Intracellular sorting and abundance of plasma membrane proteins are crucial for plants to sense and respond to environmental inputs. The reversible covalent modification by ubiquitin plays a key role in inducing adjustments in protein localization and functionality. The RING DOMAIN LIGASE family, including RGLG1, has been implicated in endocytic vacuolar cargo sorting, and this study provides evidence for their role in cargo trafficking between plasma membrane and endosomal compartments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Helge M. Magnussen, Danny T. Huang
Summary: The research compared the purification profiles of the MDM2 RING domain from various species and found that the RING domain from other species is less prone to aggregation compared to human. A single point mutation, G443T, was identified to greatly enhance the dimeric fraction of human MDM2 RING domain during purification, which will facilitate further studies and the development of new anti-cancer drugs.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
David C. Hughes, Leslie M. Baehr, David S. Waddell, Adam P. Sharples, Sue C. Bodine
Summary: The development and prevalence of diseases associated with aging have a global health burden on society. One hallmark of aging is the loss of proteostasis, partly caused by alterations to the ubiquitin-proteasome system and lysosome-autophagy system, leading to impaired function and maintenance of mass in tissues such as skeletal muscle. In skeletal muscle, functional impairment occurs early in the aging process and depends on proteostatic mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Andrew G. Manford, Elijah L. Mena, Karen Y. Shih, Christine L. Gee, Rachael McMinimy, Brenda Martinez-Gonzalez, Rumi Sherriff, Brandon Lew, Madeline Zoltek, Fernando Rodriguez-Perez, Makda Woldesenbet, John Kuriyan, Michael Rape
Summary: Oxidative phosphorylation not only produces ATP, but also generates reactive oxygen species. Cells alleviate reductive stress by ubiquitylating and degrading FNIP1, which relies on zinc as a molecular glue during this process.
Article
Multidisciplinary Sciences
Yawei Ru, Xiaojie Yan, Bing Zhang, Lili Song, Qiqi Feng, Chen Ye, Zhili Zhou, Zhenzhen Yang, Yao Li, Zhenjian Zhang, Qianqian Li, Wenyi Mi, Cheng Dong
Summary: In this study, a new C-degron pathway, called the Gln/C-degron pathway, was discovered. The B30.2 domain of TRIM7 mediates the recognition of proteins with a C-terminal glutamine. The C-terminal residues of the substrate play a crucial role in C-degron recognition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Pharmacology & Pharmacy
Si-Min Qi, Jinyun Dong, Zhi-Yuan Xu, Xiang-Dong Cheng, Wei-Dong Zhang, Jiang-Jiang Qin
Summary: PROTAC technology is an effective method for degrading target proteins through the ubiquitin-proteasome system, with promising applications in cancer treatment. The first oral PROTACs have shown encouraging results in clinical trials, sparking greater enthusiasm for PROTAC research.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lydia Qian, Laura J. Sharpe, Akira Gokool, Irina Voineagu, Andrew J. Brown
Summary: Circular RNAs (circRNAs) have various functions, and the MARCHF6 circRNA plays a crucial role in cholesterol homeostasis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2023)
Article
Oncology
Laura Kristin Esser, Vittorio Branchi, Farhad Shakeri, Adrian Georg Simon, Carsten Stephan, Glen Kristiansen, Andreas Buness, Hubert Schorle, Marieta Ioana Toma
Summary: This study investigated the effects of PARK2 overexpression in ccRCC cell lines and found that it can suppress tumor invasion and migration by regulating the expression of CKS2. It also revealed that high CKS2 levels are associated with high tumor grading and lower patient survival, suggesting CKS2 as a potential biomarker and therapeutic target for ccRCC.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Orsolya Bilkei-Gorzo, Tiaan Heunis, Jose Luis Marin-Rubio, Francesca Romana Cianfanelli, Benjamin Bernard Armando Raymond, Joseph Inns, Daniela Fabrikova, Julien Peltier, Fiona Oakley, Ralf Schmid, Anetta Hartlova, Matthias Trost
Summary: This study reveals the importance of phagosomal ubiquitylation and the E3 ubiquitin ligase RNF115 in regulating innate immune functions during bacterial infections.
Article
Oncology
Moyang Lv, Weichao Hu, Shengwei Zhang, Lijiao He, Changjiang Hu
Summary: Proteolysis-targeting chimeras (PROTACs) are a promising class of drugs that can effectively target undruggable proteins and have potential applications in cancer therapy. This review provides an overview of PROTAC technology and highlights recent clinical trials, as well as novel findings and strategies to enhance PROTAC antitumor activity.
Article
Chemistry, Medicinal
Adam G. Bond, Conner Craigon, Kwok-Ho Chan, Andrea Testa, Athanasios Karapetsas, Rotimi Fasimoye, Thomas Macartney, J. Julian Blow, Dario R. Alessi, Alessio Ciulli
Summary: This study describes the design and development of a new protein degradation system utilizing a variant of the Brd4 bromodomain as a degradation tag. The system effectively degrades BromoTagged proteins in a fast, selective manner, showing favorable pharmacokinetic profile in mice. This system expands the arsenal of chemical genetic degradation tools for manipulating protein levels and exploring therapeutic potential in cells and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Martin P. Schwalm, Lena M. Berger, Maximilian N. Meuter, James D. Vasta, Cesear R. Corona, Sandra Roehm, Benedict-Tilman Berger, Frederic Farges, Sebastian M. Beinert, Franziska Preuss, Viktoria Morasch, Vladimir V. Rogov, Sebastian Mathea, Krishna Saxena, Matthew B. Robers, Susanne Mueller, Stefan Knapp
Summary: E3 ligases play a crucial role in regulating protein homeostasis by recruiting substrate proteins to the proteasomal degradation machinery. Recent research has focused on the Baculovirus IAP Repeat (BIR) family of E3 ligases, which contain a structurally conserved but diverse protein interaction domain. The Inhibitors of Apoptosis (IAP) family, which typically have three BIR domains, are promising drug targets. However, there is currently a lack of assay tools to evaluate the selectivity of inhibitors in this target area.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yulemi Gonzalez Quesada, Luc DesGroseillers
Summary: This study investigates the degradation mechanism of RNA-binding protein STAU1 in cancer cells. The research reveals that STAU1 degradation is related to the FPL-motif protein family and inflammation-related protein MAP4K1. Through experiments, it is confirmed that TRIM25 is the E3 ubiquitin ligase responsible for the degradation of STAU1 and MAP4K1. These findings are significant for further exploration of the inflammation mechanisms associated with cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Zhongyi Yang, Yingjun Chi, Yanmei Cui, Zhen Wang, Dezhou Hu, Hui Yang, Javaid Akhter Bhat, Hui Wang, Guizhen Kan, Deyue Yu, Fang Huang
Summary: The soybean E3 ubiquitin ligase, GmRNF1a, may affect pod dehiscence and seed development through MADS family genes. These findings are significant for the study of soybean pod and seed development.
Review
Biochemistry & Molecular Biology
Rui Zhang, Shaoqing Shi
Summary: HECT-type E3 ubiquitin ligases play a vital role in controlling protein function and stability, and members of the NEDD4 family have critical roles in dysregulation of autophagy in cancer cells. This review focuses on the role of NEDD4 E3 ligases in defective autophagy in cancer cells, discussing their function, substrates, and signaling pathways, providing a basis for cancer treatment through modulation of these ligases.
MOLECULAR MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Keitaro Hayashi, Naohiko Anzai
Summary: Ingestion of amino acids plays a crucial role in cellular activities, especially in immune cell metabolic reprogramming. Transport of amino acids by transporters is essential for the progression of metabolic rewiring. Targeting amino acid transporters may offer potential for improving immune disorders and cancer immune therapies.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Review
Oncology
Xue Zhao, Shinichi Sakamoto, Maihulan Maimaiti, Naohiko Anzai, Tomohiko Ichikawa
Summary: LAT1-4F2hc complex is an important amino acid transporter involved in urological cancers. Inhibiting LAT1-4F2hc complex shows promise as a targeted therapy for these cancers.
Correction
Chemistry, Medicinal
Yudai Kudo, Satoshi Endo, Mei Fujita, Atsumi Ota, Yuji O. Kamatari, Yoshimasa Tanaka, Takeshi Ishikawa, Hayato Ikeda, Takuya Okada, Naoki Toyooka, Naohiro Fujimoto, Toshiyuki Matsunaga, Akira Ikari
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yudai Kudo, Satoshi Endo, Mei Fujita, Atsumi Ota, Yuji O. Kamatari, Yoshimasa Tanaka, Takeshi Ishikawa, Hayato Ikeda, Takuya Okada, Naoki Toyooka, Naohiro Fujimoto, Toshiyuki Matsunaga, Akira Ikari
Summary: This study discovered inhibitors of Atg4B, a key enzyme in autophagosome formation, and evaluated their potential as therapeutics for prostate cancer. Compound 17 showed the most potent Atg4B inhibitory activity and enhanced the anticancer activity of anti-CRPC drugs. Through structural optimization, compound 21f was developed as a competitive inhibitor with strong inhibitory activity against Atg4B.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Motoshi Ouchi, Asuka Morita, Keitaro Satoh, Shunsuke Kobayashi, Misao Terada, Hiroe Kon, Keitaro Hayashi, Tatsuya Suzuki, Kenzo Oba, Hitoshi Sugihara, Masahiro Yasutake, Naohiko Anzai, Tomoe Fujita
Summary: This study aimed to assess the effects of short-term stimulation with 1,5-AG on insulin secretion. The results indicated that 1,5-AG had no significant effect on insulin secretion, while stimulation with glimepiride significantly increased insulin secretion.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Naoyuki Otani, Motoshi Ouchi, Kazuharu Misawa, Ichiro Hisatome, Naohiko Anzai
Summary: Hypouricemia, a rare disorder, is divided into overexcretion and underproduction types. Renal hypouricemia, the latter type, is the most common in Japan and can increase the risk of exercise-induced acute kidney injury and urolithiasis. It is crucial to conduct research on renal hypouricemia to gain insight into its pathophysiology and develop new treatments for gout and hyperuricemia.
Article
Immunology
Takayoshi Owada, Kazuhiro Kurasawa, Hitoshi Endou, Tomoe Fujita, Naohiko Anzai, Keitaro Hayashi
Summary: The study shows that LAT1 plays a crucial role in T helper-mediated autoimmune arthritis and suggests a potential therapeutic approach targeting amino acid transporters for treating hypersensitive immune diseases.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hiroaki Eguchi, Riho Kimura, Haruka Matsunaga, Toshiyuki Matsunaga, Yuta Yoshino, Satoshi Endo, Akira Ikari
Summary: This study found that fisetin can enhance the toxicity of anticancer drugs in A549 lung adenocarcinoma spheroids by reducing CLDN2 expression, potentially through inhibiting the PI3K/Akt signaling pathway and affecting hypoxia levels in the tumor microenvironment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Yuri Hirayama, Naohiko Anzai, Hiroyuki Kinouchi, Schuichi Koizumi
Summary: Preconditioning can protect neurons against lethal ischemic injury, known as ischemic tolerance. P2X7 receptors in astrocytes play a crucial role in preconditioning, acting as a switch to protect the brain against ischemia by transforming into an ischemia-resistant phenotype.
Article
Biochemistry & Molecular Biology
Hiroaki Eguchi, Riho Kimura, Saki Onuma, Ayaka Ito, Yaqing Yu, Yuta Yoshino, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari
Summary: Claudin-2 is abnormally expressed in lung adenocarcinoma, and caffeine and theobromine can decrease its protein level, while enhancing the toxicity of doxorubicin in A549 cells. This effect may be achieved by accelerating lysosomal degradation of CLDN2 and reducing Nrf2 expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yudai Kudo, Satoshi Endo, Masatoshi Tanio, Tomofumi Saka, Rin Himura, Naohito Abe, Mitsumi Takeda, Eiji Yamaguchi, Yuta Yoshino, Yuki Arai, Hirohito Kashiwagi, Masayoshi Oyama, Akichika Itoh, Masaki Shiota, Naohiro Fujimoto, Akira Ikari
Summary: This study reveals the important roles of adrenal-derived 11-oxygenated androgens and DHRS11 in the progression of prostate cancer. It also identifies a novel DHRS11 inhibitor, KC-A, which suppresses androgen signaling and enhances the anticancer activity of a CRPC drug. These findings suggest that KC-A may be a potential candidate for the prevention and treatment of CRPC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Toshiyuki Matsunaga, Misato Horinouchi, Haruhi Saito, Aki Hisamatsu, Kazuhiro Iguchi, Yuta Yoshino, Satoshi Endo, Akira Ikari
Summary: Paclitaxel (PTX) is commonly used for breast cancer chemotherapy, but continuous treatment causes hyposensitivity. This study found that acquiring chemoresistance leads to up-regulation of aldo-keto reductase (AKR) 1C3. Inhibiting AKR1C3 and reducing its expression increased MCF7 cell sensitivity to PTX, while overexpression of AKR1C3 decreased sensitivity. The resistant cells were less sensitive to cytotoxic aldehydes derived from ROS-mediated lipid peroxidation and showed reduced levels of these aldehydes during PTX treatment. AKR1C3 inhibition mitigated this reduction, suggesting its role in the development of PTX resistance. The resistance also promoted abnormal expression of ABC transporter ABCB1, and combined treatment with AKR1C3 and ABCB1 inhibitors overcame PTX resistance and cross-resistance to docetaxel.
JOURNAL OF BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Satoshi Endo, Yoshifumi Morikawa, Toshiyuki Matsunaga, Akira Hara, Masaki Takasu
Summary: A porcine gene, LOC100622246, encodes carbonyl reductase [NADPH] 1 (pCBR-N1), whose function remains unknown. Previously, three porcine carbonyl reductases, carbonyl reductase 1 (pCBR1), 3 alpha/ss-hydroxysteroid dehydrogenase (p3 alpha/ss-HSD) and prostaglandine-9-keto reductase (pPG-9-KR), were purified from different pig tissues. The relationship between pCBR-N1 and these three enzymes is still unknown. This study compared the properties of pCBR-N1 and pCBR1 and found that pCBR-N1 is identical to p3 alpha/ss-HSD and pPG-9-KR. pCBR-N1 is a glutathione-activated carbonyl reductase that functions in the metabolism of endogenous and xenobiotic carbonyl compounds.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Medicine, Research & Experimental
Asuka Morita, Motoshi Ouchi, Keitaro Satoh, Shunsuke Kobayashi, Misao Terada, Hidefumi Wakashin, Hiroe Kon, Keitaro Hayashi, Naohiko Anzai, Akira Shimizu, Hitoshi Sugihara, Kenzo Oba, Tomoe Fujita
Summary: The study found that even low concentrations of trypsin inhibitor can maintain insulin secretion in organ bath experiments by inhibiting trypsin activity. This research result provides an important experimental basis for further studies on pancreas-related diseases.
Meeting Abstract
Biochemistry & Molecular Biology
Asuka Morita, Motoshi Ouchi, Keitaro Satoh, Shunsuke Kobayashi, Naohiko Anzai, Akira Shimizu, Hitoshi Sugihara, Kenzo Oba, Tomoe Fujita