Article
Cell Biology
Manuel Olazabal-Moran, Miriam Sanchez-Ortega, Laura Martinez-Munoz, Carmen Hernandez, Manuel S. Rodriguez, Mario Mellado, Ana C. Carrera
Summary: PI3-kinase and PTEN regulate the PIP3/AKT signaling pathway through the ubiquitin ligase cCBL, influencing cell survival, division, and migration. These findings reveal a novel mechanism for PI3-kinase/PTEN crosstalk and suggest that cCBL may be a potential target for modulating PTEN activity in cancer.
Review
Biochemistry & Molecular Biology
Ahmad Perwez, Khushnuma Wahabi, Moshahid A. Rizvi
Summary: Parkin, an E3 ubiquitin ligase, is deregulated in various human cancers and plays a crucial role in cancer pathogenesis by controlling major cancer hallmarks. Dysfunction of Parkin leads to genomic instability, perturbed cell cycle, and tumor progression. Existing studies highlight the tumor suppressive potential of Parkin, emphasizing its therapeutic implications and value as a biomarker.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Review
Oncology
Ganghui Ye, Jie Wang, Weili Yang, Jinyun Li, Meng Ye, Xiaofeng Jin
Summary: The KLHL family members regulate tumorigenesis and progression through ubiquitination of target substrates, but the regulation and interactions of other KLHL family members are still unclear.
AMERICAN JOURNAL OF CANCER RESEARCH
(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
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)
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
Immunology
Haoran Cui, Yaxian Zhang, Leiliang Zhang
Summary: Poxviruses have evolved various mechanisms to evade innate immunity, some of which involve poxvirus-encoded E3 ubiquitin ligases and adaptor proteins. These proteins can be categorized into five groups based on their functional domains and ubiquitin transfer mechanisms. Most known substrates of poxvirus E3 ubiquitin ligases are components of the innate immune system. Current research progress provides mechanistic insights into the interaction between these viruses and their hosts.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Plant Sciences
Jialing Zhang, Chaonan Li, Long Li, Yajun Xi, Jingyi Wang, Xinguo Mao, Ruilian Jing
Summary: TaAIRP2-1B regulates spike length by facilitating TaHIPP3 degradation, and the haplotype Hap-1B-1 of TaAIRP2-1B is a favorable natural variation for increasing spike length in wheat. This study provides insights into the role of E3 ubiquitin ligase genes in wheat development and identifies TaAIRP2-1B as a key regulator of spike length. The findings also offer genetic resources and markers for wheat molecular breeding.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Review
Biochemistry & Molecular Biology
Ishita Tripathi-Giesgen, Christian Behrends, Arno F. Alpi
Summary: The ubiquitin system plays a crucial role in the host cellular defense program against bacterial infection, especially when certain bacteria are exposed to the host cytosol during invasion. Host cell E3 ubiquitin ligases contribute to the formation of a protective ubiquitin coat on invading pathogens, with their divergent ubiquitin conjugation mechanisms influencing the complexity of the anti-bacterial coating. Bacteria have evolved strategies to evade the activities of the host ubiquitin system.
Review
Biochemistry & Molecular Biology
Dong Wang, Yuanming Zou, Xinyue Huang, Zeyu Yin, Mohan Li, Jiaqi Xu, Boquan Wu, Da Li, Ying Zhang, Yingxian Sun, Xingang Zhang, Naijin Zhang
Summary: The ubiquitin-proteasome system is crucial for regulating protein levels in cells, and SMURF1 and SMURF2 are important components that maintain physiological processes by regulating the stability of multiple proteins. The regulatory functions of SMURFs in disease progression are complex, either facilitative or inhibitory, and understanding their mechanisms offers potential therapeutic targets and new avenues for research.
Review
Biochemistry & Molecular Biology
Dong Wang, Yuanming Zou, Xinyue Huang, Zeyu Yin, Mohan Li, Jiaqi Xu, Boquan Wu, Da Li, Ying Zhang, Yingxian Sun, Xingang Zhang, Naijin Zhang
Summary: The ubiquitin-proteasome system plays a crucial role in regulating protein levels in cells. SMURF1 and SMURF2 are key components in this system, responsible for regulating protein stability and maintaining physiological processes such as cell migration, proliferation, and apoptosis. They also play significant roles in disease progression, with complex regulatory functions. This review focuses on the mechanisms by which SMURF1 and SMURF2 regulate disease progression in non-cancerous diseases, providing potential therapeutic targets for various diseases and new research avenues for SMURF proteins.
Article
Biochemistry & Molecular Biology
Yi Zheng, Jian Deng, Lulu Han, Meng-Wei Zhuang, Yanwen Xu, Jing Zhang, Mei-Ling Nan, Yang Xiao, Peng Zhan, Xinyong Liu, Chengjiang Gao, Pei-Hui Wang
Summary: This study reveals the involvement of the stress response pathway and innate antiviral immunity in the pathogenic mechanism of SARS-CoV-2. NSP5 and N protein of SARS-CoV-2 were found to attenuate the formation of antiviral stress granules (avSG). NSP5 suppressed avSG formation and disrupted the RIG-I-MAVS complex to weaken the RIG-I-mediated antiviral response, while N protein specifically targeted cofactors upstream of RIG-I and affected the recognition of dsRNA by RIG-I.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Chemistry, Multidisciplinary
Fang Liu, Xuan Wang, Jianli Duan, Zhijie Hou, Zhouming Wu, Lingling Liu, Hanqi Lei, Dan Huang, Yifei Ren, Yue Wang, Xinyan Li, Junxiao Zhuo, Zijian Zhang, Bin He, Min Yan, Huiming Yuan, Lihua Zhang, Jinsong Yan, Shijun Wen, Zifeng Wang, Quentin Liu
Summary: This study introduces a PROTAC cocktail that effectively degrades AURKA in acute myeloid leukemia cells, inhibits AML stem cells, and induces AML regression in mouse models and primary patient cells. This spatial-temporal drug administration strategy shows promise in eliminating the multifaceted functions of oncoproteins and preventing cancer stem cell-mediated drug resistance.
Article
Biochemistry & Molecular Biology
Qian Lv, Liqun Li, Ying Meng, Huimin Sun, Liuping Chen, Bingxin Wang, Xuejun Li
Summary: The study revealed that TaGW2-6A interacts with TaAGPS and degrades TaAGPS through the 26S proteasome pathway, influencing seed size. This mechanism provides new insights into the formation of wheat grain weight.
Article
Oncology
Rieko Taniguchi, Hideki Muramatsu, Yusuke Okuno, Taro Yoshida, Manabu Wakamatsu, Motoharu Hamada, Chiyoe Shirota, Wataru Sumida, Akinari Hinoki, Takahisa Tainaka, Yoshimitsu Gotoh, Toyonori Tsuzuki, Yukichi Tanaka, Seiji Kojima, Hiroo Uchida, Yoshiyuki Takahashi
Summary: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by germline variants in the fumarate hydratase (FH) gene. A seven-year-old boy with a large right kidney tumor underwent nephrectomy and recovered well without metastasis or recurrence, making him the youngest-onset case of HLRCC-associated RCC reported to date. This case may impact future RCC surveillance programs for patients with HLRCC.
Article
Multidisciplinary Sciences
Takahiro Imaizumi, Julia Meyer, Manabu Wakamatsu, Hironobu Kitazawa, Norihiro Murakami, Yusuke Okuno, Taro Yoshida, Daichi Sajiki, Asahito Hama, Seiji Kojima, Yoshiyuki Takahashi, Mignon Loh, Elliot Stieglitz, Hideki Muramatsu
Summary: This study used machine learning algorithms to classify patients with Juvenile myelomonocytic leukemia (JMML) and predict their survival outcomes. The results demonstrated that the machine learning models had high accuracy in predicting patient survival, enabling rapid selection of appropriate treatment strategies following diagnosis.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Shuichi Ozono, Kazuo Sakashita, Nao Yoshida, Harumi Kakuda, Kenichiro Watanabe, Miho Maeda, Yasushi Ishida, Atsushi Manabe, Takashi Taga, Hideki Muramatsu
Summary: In this study, a questionnaire was used to investigate the late effects in survivors of allogenic hematopoietic stem cell transplantation (HSCT) for juvenile myelomonocytic leukemia (JMML). The results showed that approximately 83% of the survivors experienced more than one late effect, including endocrine, dental, skin, ophthalmologic, musculoskeletal, pulmonary, neurocognitive, and cardiovascular dysfunction. The prevalence of short stature, pulmonary, cardiovascular, and nephrological complications was significantly higher among survivors who were more than 12 years post-HSCT. Therefore, establishing a multidisciplinary follow-up system for survivors of JMML is crucial.
PEDIATRIC BLOOD & CANCER
(2023)
Letter
Hematology
Ayako Yamamori, Motoharu Hamada, Hideki Muramatsu, Manabu Wakamatsu, Asahito Hama, Atsushi Narita, Yusuke Tsumura, Taro Yoshida, Takehiko Doi, Kazuki Terada, Takeshi Higa, Nobuyuki Yamamoto, Hiroki Miura, Mitsutaka Shiota, Kenichiro Watanabe, Nao Yoshida, Ryo Maemura, Masayuki Imaya, Shunsuke Miwata, Kotaro Narita, Shinsuke Kataoka, Rieko Taniguchi, Kyogo Suzuki, Nozomu Kawashima, Nobuhiro Nishio, Hideto Iwafuchi, Masafumi Ito, Seiji Kojima, Yusuke Okuno, Yoshiyuki Takahashi
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Medicine, General & Internal
Sosuke Arakawa, Makoto Nakao, Kazuki Sone, Shuntaro Hayashi, Masahiro Sugihara, Yuya Hirata, Mamiko Kuriyama, Norihisa Takeda, Kazuhiro Ohtakara, Yoshimi Horikawa, Hideki Muramatsu
Summary: A 77-year-old man presented with cough, pharyngeal discomfort, and weight loss for 1 month. Chest radiography showed a mass shadow in the right upper lung field. Bronchoscopy revealed multiple white nodules along the tracheal cartilage ring. Adenocarcinoma cells were detected in the mass, but no malignancy was found in several biopsy specimens of the tracheal lesions. F-18-fluorodeoxyglucose positron emission tomography showed intense accumulation in the mass, nasal septum, and tracheal cartilage. Furthermore, the patient had elevated levels of anti-type II collagen antibody. He was finally diagnosed with lung cancer complicated by relapsing polychondritis. The treatment included oral prednisolone and sequential chemoradiotherapy for lung cancer.
Article
Hematology
Motoharu Hamada, Hideki Muramatsu, Yuka Torii, Kyogo Suzuki, Atsushi Narita, Taro Yoshida, Masayuki Imaya, Ayako Yamamori, Manabu Wakamatsu, Shunsuke Miwata, Kotaro Narita, Shinsuke Kataoka, Nozomu Kawashima, Rieko Taniguchi, Eri Nishikawa, Nobuhiro Nishio, Yoshinori Ito, Seiji Kojima, Yoshiyuki Takahashi
Summary: This single-center retrospective study evaluated the outcomes of 30 children who underwent bone marrow transplantation from HLA 7/8-matched unrelated donors with rATG as GVHD prophylaxis. The results showed favorable outcomes and acceptable GVHD, indicating the feasibility of this approach.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2023)
Review
Hematology
Taro Fukuta, Hideki Muramatsu, Daiki Yamashita, Daichi Sajiki, Ryo Maemura, Yusuke Tsumura, Ayako Yamamori, Masayuki Imaya, Manabu Wakamatsu, Eri Nishikawa, Kotaro Narita, Shinsuke Kataoka, Rieko Taniguchi, Atsushi Narita, Nobuhiro Nishio, Yoshiyuki Takahashi
Summary: This article presents a case study of vedolizumab treatment for pediatric intestinal acute graft-versus-host disease (aGVHD). The efficacy of vedolizumab in 10 pediatric patients with intestinal aGVHD was evaluated, and the results showed potential effectiveness of this drug with no serious adverse events.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Asuka Kono, Manabu Wakamatsu, Yoshihiro Umezawa, Hideki Muramatsu, Hiroki Fujiwara, Dan Tomomasa, Kento Inoue, Keiichiro Hattori, Tetsuo Mitsui, Hidetoshi Takada, Yoshiyuki Minegishi, Yoshiyuki Takahashi, Masahide Yamamoto, Takehiko Mori, Hirokazu Kanegane
Summary: DOCK8 deficiency is a rare genetic immune deficiency characterized by eczema, elevated IgE, and recurrent infections. Two Japanese patients with DOCK8 deficiency were successfully treated by allogeneic HCT from alternative donors, resulting in improved clinical manifestations and successful engraftment and immune reconstitution.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2023)
Article
Pathology
Kazunori Haruta, Suguru Takeuchi, Makoto Yamaguchi, Kazuhiro Horiba, Takako Suzuki, Yuka Torii, Atsushi Narita, Hideki Muramatsu, Yoshiyuki Takahashi, Yoshinori Ito, Jun-ichi Kawada
Summary: In this study, a novel pathogen detection technology called droplet digital PCR (ddPCR) was developed and compared with real-time quantitative PCR (qPCR) for detecting human adenovirus DNA. The results showed that ddPCR exhibited better reproducibility and sensitivity, as well as equivalent quantifiability, compared with qPCR. Therefore, ddPCR has the potential to provide a more accurate DNAemia detection, determine cutoff values for treatment initiation, and enable antiviral efficacy assessment.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2023)
Article
Oncology
Shinsaku Imashuku, Shin-ichiro Suemori, Manabu Wakamatsu, Yusuke Okuno, Hideki Muramatsu, Shigeru Makino, Takashi Miyoshi, Kazuhisa Chonabayashi, Hitoshi Kanno
Summary: Differential diagnosis of juvenile hemochromatosis with hemolytic anemia is challenging. We present a case of a 23-year-old woman with macrocytic hemolytic anemia and iron overload. A mutation in the PIEZO1 gene (heterozygous c.6008C>A: p.A2003D) was identified through target gene sequencing, which has been previously reported in a family with dehydrated hereditary stomatocytosis (DHS1, [OMIM 194380]). This case highlights the importance of considering DHS1 in the differential diagnosis of iron overload associated with non-transfused hemolytic anemia in children and young adults.
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
(2023)
Letter
Oncology
Hiromi Tobai, Mikiya Endo, Masataka Ishimura, Kunihiko Moriya, Jun Yano, Keita Kanamori, Norio Sato, Fumitaka Amanuma, Hidekazu Maruyama, Hideki Muramatsu, Junji Shibahara, Masami Narita, Seiko Fumoto, Daniel Peltier, Shouichi Ohga
PEDIATRIC BLOOD & CANCER
(2023)
Article
Clinical Neurology
Hiroyuki Yamamoto, Jun Natsume, Kimihiko Kaneko, Toshiyuki Takahashi, Manabu Wakamatsu, Chikako Ogawa, Sumire Kumai, Ryosuke Suzui, Fumi Sawamura, Anna Shiraki, Tomohiko Nakata, Hiroyuki Kidokoro, Hideki Muramatsu, Yoshiyuki Takahashi
Summary: This study reports two rare cases of patients with juvenile myelomonocytic leukemia (JMML) who developed myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We propose that abnormalities in the RAS pathway contribute to the formation of anti-MOG antibodies and the onset of MOGAD.
PEDIATRIC NEUROLOGY
(2023)
Article
Cell & Tissue Engineering
Ryo Maemura, Manabu Wakamatsu, Kana Matsumoto, Hirotoshi Sakaguchi, Nao Yoshida, Asahito Hama, Taro Yoshida, Shunsuke Miwata, Hironobu Kitazawa, Kotaro Narita, Shinsuke Kataoka, Daisuke Ichikawa, Motoharu Hamada, Rieko Taniguchi, Kyogo Suzuki, Nozomu Kawashima, Eri Nishikawa, Atsushi Narita, Yusuke Okuno, Nobuhiro Nishio, Koji Kato, Seiji Kojima, Kunihiko Morita, Hideki Muramatsu, Yoshiyuki Takahashi
Summary: This study aims to investigate the relationship between the pharmacokinetics of melphalan and transplantation outcomes in children and develop a predictive model for melphalan clearance. The results suggest that adjusting the melphalan dose according to urinary creatinine excretion rate and creatinine clearance rate may optimize its exposure.
CELL TRANSPLANTATION
(2022)
Meeting Abstract
Biophysics
C. Tono, A. Tanizawa, A. Watanabe, M. Ito, H. Shima, Y. Yuza, H. Muramatsu, M. Okada, H. Shimada
BONE MARROW TRANSPLANTATION
(2022)
Meeting Abstract
Oncology
Dai Keino, Akihiko Tanizawa, Akihiro Watanabe, Masaki Ito, Chikako Tono, Haruko Shima, Yuki Yuza, Hideki Muramatsu, Hiroyuki Shimada
PEDIATRIC BLOOD & CANCER
(2022)