Article
Oncology
Mingjue Chen, Tetsuo Mashima, Taichi Oishi, Yukiko Muramatsu, Yosuke Seto, Manabu Takamatsu, Naomi Kawata, Shun Morino, Ayane Nakamura, Saori Inaba, Xunmei Yuan, Kohei Maruyama, Mai Suzuki, Ayana Sato, Haruka Yoshida, Myung-Kyu Jang, Anna Mizutani, Kengo Takeuchi, Kensei Yamaguchi, Fumiyuki Shirai, Satoshi Nagayama, Ryohei Katayama, Hiroyuki Seimiya
Summary: APC/PIK3CA mutations and beta-catenin can predict the sensitivity of APC-mutated CRC PDCs to tankyrase inhibitors, providing potential biomarkers for patient selection in future clinical trials. PIK3CA mutations were found to be more frequent in inhibitor-resistant PDCs, while some wild-type APC PDCs showed sensitivity to inhibitors in a beta-catenin-independent manner.
BRITISH JOURNAL OF CANCER
(2023)
Article
Chemistry, Medicinal
Hans-Peter Buchstaller, Uwe Anlauf, Dieter Dorsch, Sarah Kogler, Daniel Kuhn, Martin Lehmann, Birgitta Leuthner, Sara Lodholz, Djordje Musil, Daniela Radtki, Corinna Rettig, Claudio Ritzert, Felix Rohdich, Richard Schneider, Ansgar Wegener, Stefan Weigt, Kai Wilkinson, Christina Esdar
Summary: This study described the optimization process of a screening hit series, leading to the identification of compound M2912 with excellent TNKS potency, exquisite PARP selectivity, and predicted human PK compatible with once daily oral dosing. This compound demonstrated modulation of cellular Wnt pathway activity and significant tumor growth inhibition in colorectal xenograft models.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Jerome Perrard, Susan Smith
Summary: Tankyrase 1 and 2 are regulated by RNF146-mediated K48-linked polyubiquitylation and degradation. The authors discovered a novel interaction between tankyrase and the RING-UIM family of E3 ligases. They found that RNF114 and RNF166 bind and stabilize monoubiquitylated tankyrase and promote K11-linked diubiquitylation. This process competes with RNF146-mediated degradation, leading to the stabilization of tankyrase and its binding partner Angiomotin.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Katharina Klement, Martina Brueckner, Dominic B. Bernkopf
Summary: Axin serves as a negative regulator of the Wnt/β-catenin signaling pathway, and its stability is regulated by phosphorylation and degradation. Understanding the mechanisms of Axin regulation has implications for cancer therapy and biomolecular condensate organization.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Kibrom M. Alula, Yaritza Delgado-Deida, Dakota N. Jackson, K. Venuprasad, Arianne L. Theiss
Summary: PHB1 plays a role in inhibiting the Wnt/β-catenin pathway to influence the development of intestinal tumorigenesis by regulating AXIN1 expression and the beta-catenin destruction complex. Induction of nuclear PHB1 trafficking provides a novel therapeutic option to influence AXIN1 expression and the beta-catenin destruction complex in Wnt-driven intestinal tumorigenesis.
Article
Pathology
Michael Torbenson, Chantal E. McCabe, Daniel R. O'Brien, Jun Yin, Tiffany Bainter, Nguyen H. Tran, Saba Yasir, Zongming Eric Chen, Renu Dhanasekaran, Keun Soo Ahn, Lewis R. Roberts, Chen Wang
Summary: The study found that HCC with CTNNB1 mutations exhibit morphological heterogeneity, with gene penetrance for morphology dependent on gender, specific CTNNB1 mutations, and co-occurring TP53 mutations. This heterogeneity has important implications for the classification of HCC.
Article
Multidisciplinary Sciences
Chen Shen, Anmada Nayak, Leif R. Neitzel, Amber A. Adams, Maya Silver-Isenstadt, Leah M. Sawyer, Hassina Benchabane, Huilan Wang, Nawat Bunnag, Bin Li, Daniel T. Wynn, Fan Yang, Marta Garcia-Contreras, Charles H. Williams, Sivanesan Dakshanamurthy, Charles C. Hong, Nagi G. Ayad, Anthony J. Capobianco, Yashi Ahmed, Ethan Lee, David J. Robbins
Summary: This study reveals how the Wnt ligand can enhance CRBN-dependent protein degradation and highlights the importance of CRBN in physiological Wnt signaling.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Qiaoni Shi, Kexin Kang, Ye-Guang Chen
Summary: The intracellular multiprotein complex beta-catenin destruction complex is essential for Wnt/beta-catenin signaling, with recent studies showing the importance of liquid-liquid phase separation (LLPS) of Axin and APC in regulating this pathway. Post-translational modifications also play a role in the regulation of Axin LLPS.
Article
Oncology
Shoshy A. Brinch, Enya Amundsen-Isaksen, Sandra Espada, Clara Hammarstrom, Aleksandra Aizenshtadt, Petter A. Olsen, Lone Holmen, Merete Hoyem, Hanne Scholz, Gunnveig Grodeland, Sven T. Sowa, Albert Galera-Prat, Lari Lehtio, Ilonka A. T. M. Meerts, Ruben G. G. Leenders, Anita Wegert, Stefan Krauss, Jo Waaler
Summary: In this study, the researchers developed a novel TNKS1/2 inhibitor called OM-153, which effectively reduced WNT/β-catenin signaling and showed antitumor effects in colon carcinoma and melanoma models. OM-153 demonstrated a therapeutic window and minimal toxicity to the intestines and other organs.
CANCER RESEARCH COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Nisha Pillay, Laura Mariotti, Mariola Zaleska, Oviya Inian, Matthew Jessop, Sam Hibbs, Ambroise Desfosses, Paul C. R. Hopkins, Catherine M. Templeton, Fabienne Beuron, Edward P. Morris, Sebastian Guettler
Summary: This research reveals the structure of the active unit filament of tankyrase and shows how its catalytic and non-catalytic functions are controlled by polymerization. The cryo-electron microscopy reconstruction provides detailed insights into the interactions between the SAM domain and the catalytic domain, as well as the role of head-to-head and tail-to-tail interactions at the active site.
Review
Cell Biology
Chenchen Li, Emma E. Furth, Anil K. Rustgi, Peter S. Klein
Summary: The Wnt signaling pathway is crucial in metazoan development and stem cell maintenance, and is also involved in various malignancies. Apart from the canonical activation, the pathway can affect cell function through multiple alternative effectors, potentially contributing to cancer development.
Article
Multidisciplinary Sciences
Line Mygland, Shoshy Alam Brinch, Martin Frank Strand, Petter Angell Olsen, Aleksandra Aizenshtadt, Kaja Lund, Nina Therese Solberg, Max Lycke, Tor Espen Thorvaldsen, Sandra Espada, Dorna Misaghian, Christian M. Page, Oleg Agafonov, Stale Nygard, Nai-Wen Chi, Eva Lin, Jenille Tan, Yihong Yu, Mike Costa, Stefan Krauss, Jo Waaler
Summary: Small-molecule tankyrase 1 and tankyrase 2 (TNKS1/2) inhibitors have shown to be effective antitumor agents in specific tumor cell lines, with the ability to inhibit key signaling pathways and reduce expression of crucial oncogenes, ultimately impairing cell growth. Additionally, these inhibitors induce the accumulation of beta-catenin degradasomes containing TNKS1/2, which interact with YAP and angiomotin proteins, leading to attenuation of YAP signaling. Further research is needed to fully evaluate the potential of TNKS inhibitors in cancer treatment.
Article
Multidisciplinary Sciences
Ana R. Moshkovsky, Marc W. Kirschner
Summary: Axin is a crucial protein in the canonical Wnt pathway, and its differential regulation allows for tissue-specific functions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Yoshinori Matsumoto, Ioannis D. Dimitriou, Jose La Rose, Melissa Lim, Susan Camilleri, Napoleon Law, Hibret A. Adissu, Jiefei Tong, Michael F. Moran, Andrzej Chruscinski, Fang He, Yosuke Asano, Takayuki Katsuyama, Ken-Ei Sada, Jun Wada, Robert Rottapel
Summary: This study demonstrates that tankyrase negatively regulates TLR2 signaling, and its deficiency leads to systemic inflammation and elevated inflammatory cytokine production. Mechanistically, tankyrase deficiency results in tyrosine phosphorylation and activation of TLR2, which relies on the kinases SRC and SYK. Additionally, the observed inflammation and cytokine production in the absence of tankyrase are dependent on the adaptor protein 3BP2.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Rui Zhang, Shuai Yu, Qiaoyan Shen, Wenxu Zhao, Juqing Zhang, Xiaolong Wu, Zhenshuo Zhu, Xiaojie Wu, Na Li, Sha Peng, Jinlian Hua
Summary: The study discovered that overexpression of the porcine AXIN2 gene significantly decreased the survival and pluripotency of piPSCs, while knockdown of AXIN2, a negative effector of the WNT signaling pathway, enhanced genes related to cell cycle but reduced genes associated with cell differentiation, death, and apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Developmental Biology
Zhenghan Wang, Ai Tian, Hassina Benchabane, Ofelia Tacchelly-Benites, Eungi Yang, Hisashi Nojima, Yashi Ahmed
Article
Biochemistry & Molecular Biology
Zeinab Anvarian, Hisashi Nojima, Eline C. van Kappel, Tobias Madl, Maureen Spit, Martin Viertler, Ingrid Jordens, Teck Y. Low, Revina C. van Scherpenzeel, Ineke Kuper, Klaus Richter, Albert J. R. Heck, Rolf Boelens, Jean-Paul Vincent, Stefan G. D. Rudiger, Madelon M. Maurice
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2016)
Article
Multidisciplinary Sciences
Eungi Yang, Ofelia Tacchelly-Benites, Zhenghan Wang, Michael P. Randall, Ai Tian, Hassina Benchabane, Sarah Freemantle, Claudio Pikielny, Nicholas S. Tolwinski, Ethan Lee, Yashi Ahmed
NATURE COMMUNICATIONS
(2016)
Article
Genetics & Heredity
Zhenghan Wang, Ofelia Tacchelly-Benites, Eungi Yang, Yashi Ahmed
Article
Genetics & Heredity
Ai Tian, Hassina Benchabane, Zhenghan Wang, Yashi Ahmed
Article
Genetics & Heredity
Ai Tian, Hassina Benchabane, Zhenghan Wang, Chloe Zimmerman, Nan Xin, Jessica Perochon, Gabriela Kalna, Owen J. Sansom, Chao Cheng, Julia B. Cordero, Yashi Ahmed
Article
Genetics & Heredity
Ofelia Tacchelly-Benites, Zhenghan Wang, Eungi Yang, Hassina Benchabane, Ai Tian, Michael P. Randall, Yashi Ahmed
Article
Genetics & Heredity
Zhenghan Wang, Ofelia Tacchelly-Benites, Geoffrey P. Noble, Megan K. Johnson, Jean-Philippe Gagne, Guy G. Poirier, Yashi Ahmed
Article
Cell Biology
Carles Recasens-Alvarez, Cyrille Alexandre, Joanna Kirkpatrick, Hisashi Nojima, David J. Huels, Ambrosius P. Snijders, Jean-Paul Vincent
Summary: Ribosomes are essential molecular machines for protein synthesis, and deficiencies in ribosomal proteins can lead to proteotoxic stress and cell apoptosis. Modulating the integrated stress response and autophagy can affect the severity of ribosomal protein deficiency-induced harm, suggesting potential cytoprotective strategies for ribosomopathies.
NATURE CELL BIOLOGY
(2021)
Article
Medical Laboratory Technology
Rikei Kozakai, Akira Kushida, Paul Franck Adeyissimi Adjou Moumouni, Sadatsugu Okuma, Kazuya Takahashi, Kuniko Hoshi, Yuri Sato, Mizue Takahashi, Nodoka Chida, Mei Takahashi, Shukuko Iwabuchi, Yoshihiko Izumi, Kana Fukami, Shuji Nakashiro, Hisashi Nojima, Shinichiro Takahashi
Summary: This study examined the levels of SARS-CoV-2 antibodies in Japanese volunteers who received the BNT162b2 vaccine and evaluated the humoral responses and side effects. The results showed a significant increase in IgM and IgG levels after vaccination, but these responses declined with age. The commonly reported side effects included sore arm/pain, generalized weakness/fatigue, and fever.
JOURNAL OF LABORATORY MEDICINE
(2022)
Article
Infectious Diseases
Hidetoshi Nomoto, Kei Yamamoto, Erina Isaka, Yusuke Miyazato, Tetsuya Suzuki, Taketomo Maruki, Gen Yamada, Kohei Kamegai, Yutaro Akiyama, Satoshi Ide, Masami Kurokawa, Ataru Moriya, Kazuhisa Mezaki, Shintaro Yagi, Hisashi Nojima, Kentaro Yamakawa, Norio Ohmagari
Summary: This study investigated the feasibility and accuracy of rapid antigen tests for anterior nasal (AN) sampling compared to nasopharyngeal (NP) sampling for diagnosing coronavirus disease. The results showed that ESP, LUMI, and LUMI-P had practical diagnostic accuracy for AN sampling and there were no significant factors affecting the concordance between AN and NP sampling.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2023)
Article
Clinical Neurology
Hisashi Nojima, Satoshi Ito, Akira Kushida, Aki Abe, Wataru Motsuchi, David Verbel, Manu Vandijck, Geert Jannes, Ina Vandenbroucke, Katsumi Aoyagi
Summary: This study examined the relationship between cerebrospinal fluid (CSF) biomarkers and brain beta-amyloid (Aβ) deposition using amyloid positron emission tomography (PET). The results showed good agreement between CSF biomarkers measured with the LUMIPULSE system and amyloid PET imaging. The ratio of Aβ42 with other biomarkers showed a higher correlation with amyloid PET than Aβ42 alone, suggesting potential value in diagnostic assessment and routine clinical practice.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)