Wnt/Wingless (Wg) signaling is critical in development and disease, including cancer. Canonical Wnt signaling is mediated by β-catenin/Armadillo (Arm in Drosophila) transducing signals to the nucleus, with IFT-A/Kinesin 2 complexes promoting nuclear translocation of β-catenin/Arm. Here, we demonstrate that a conserved small N-terminal Arm/β-catenin peptide binds to IFT140, acting as a dominant interference tool to attenuate Wg/Wnt signaling in vivo. Arm expression antagonizes endogenous Wnt/Wg signaling, resulting in the reduction of its target expression. Arm inhibits Wg/Wnt signaling by interfering with nuclear translocation of endogenous Arm/β-catenin, and this can be modulated by levels of wild-type β-catenin or IFT140, with the Arm effect being enhanced or suppressed. Importantly, this mechanism is conserved in mammals with the equivalent β-catenin peptide blocking nuclear translocation and pathway activation, including in cancer cells. Our work indicates that Wnt signaling can be regulated by a defined N-terminal β-catenin peptide and thus might serve as an entry point for therapeutic applications to attenuate Wnt/β-catenin signaling.
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http://dx.doi.org/10.1016/j.celrep.2024.114362 | DOI Listing |
Drug Des Devel Ther
January 2025
Department of Hepatobiliary Surgery, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, People's Republic of China.
Introduction: Oxidative stress is an important cause of acetaminophen (APAP)-induced liver injury (AILI). Sakuranetin (Sak) is an antitoxin from the cherry flavonoid plant with good antioxidant effects. However, whether sakuranetine has a protective effect on APAP-induced liver injury is not clear.
View Article and Find Full Text PDFBr J Pharmacol
January 2025
Institute of Neurobiology, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Background And Purpose: Autophagy-lysosomal pathway dysfunction leads to postoperative cognitive dysfunction (POCD). Dexmedetomidine (Dex) improves POCD, and we probed the effects of Dex on autophagy-lysosomal pathway dysfunction in a POCD model.
Experimental Approach: A POCD mouse model was established and intraperitoneally injected with Dex.
Sci Rep
January 2025
Department of Bioscience and Biotechnology, Konkuk University, Seoul, 05029, Republic of Korea.
Exposure to particulate matter (PM) in the air harms human health. Most studies on particulate matter's (PM) effects have primarily focused on respiratory and cardiovascular diseases. Recently, IL-32θ, one of the IL-32 isoforms, has been demonstrated to modulate cancer development and inflammatory responses.
View Article and Find Full Text PDFNat Commun
January 2025
Laboratory of Pathogens and Host Immunity, UMR 5294 CNRS, UA15 INSERM, Université de Montpellier, Montpellier, 34095, France.
Programmed-cell death is an antimicrobial defense mechanism that promotes clearance of intracellular pathogens. Toxoplasma counteracts host immune defenses by secreting effector proteins into host cells; however, how the parasite evades lytic cell death and the effectors involved remain poorly characterized. We identified ROP55, a rhoptry protein that promotes parasite survival by preventing lytic cell death in absence of IFN-γ stimulation.
View Article and Find Full Text PDFLife Sci Alliance
March 2025
https://ror.org/00hj54h04 Interdisciplinary Life Sciences Graduate Programs, The University of Texas at Austin, Austin, TX, USA
Breast cancer stem cells (CSCs) are difficult to therapeutically target, but continued efforts are critical given their contribution to tumor heterogeneity and treatment resistance in triple-negative breast cancer. CSC properties are influenced by metabolic stress, but specific mechanisms are lacking for effective drug intervention. Our previous work on TFEB suggested a key function in CSC metabolism.
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