Targeted protein degradation (TPD) utilizes molecular glues or proteolysis-targeting chimeras (PROTACs) to eliminate disease-causing proteins by promoting their interaction with E3 ubiquitin ligases. Current TPD approaches are limited by reliance on a small number of constitutively active E3 ubiquitin ligases. Here, we report that (S)-ACE-OH, a metabolite of the antipsychotic drug acepromazine, acts as a molecular glue to induce an interaction between the E3 ubiquitin ligase TRIM21 and the nucleoporin NUP98, leading to the degradation of nuclear pore proteins and disruption of nucleocytoplasmic trafficking.
View Article and Find Full Text PDFIn the field of physics and materials science, the discovery of the layer-polarized anomalous Hall effect (LP-AHE) stands as a crucial development. The current research paradigm is rooted in topological or inversion-asymmetric valleytronic systems, making such a phenomenon rather rare. In this work, a universal design principle for achieving the LP-AHE from inversion-symmetric single-layer lattices is proposed.
View Article and Find Full Text PDFElectro-mechanical coupling is of great interest for applications in sensors, actuators and energy harvesters. While the control of electrical charge by mechanical force has been studied extensively, reverse coupling is rarely explored, especially in two-dimensional (2D) lattices. Herein, we propose a novel mechanism for electro-mechanical coupling that realizes the electric field switching of the dimensions of a 2D lattice in a reversible and nonvolatile fashion, through the mediated strength of interlayer interactions in ferroelectric bilayer systems.
View Article and Find Full Text PDFThe layer-polarized anomalous Hall effect (LP-AHE), derived from the coupling between the Berry curvature and the layer degree of freedom, is of importance for both fundamental physics and device applications. Nonetheless, the current research paradigm is rooted in topological systems, rendering such a phenomenon rather scarce. Here, through model analysis, we propose an alternative, but general, mechanism for realizing the LP-AHE in valleytronic van der Waals bilayers by interlayer sliding.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2022
Aberrant fibroblast growth factor 19 (FGF19) signaling mediated by its receptor, FGF receptor 4 (FGFR4), and coreceptor, klotho β (KLB), is a driver of hepatocellular carcinoma (HCC). Several potent FGFR4-selective inhibitors have been developed but have exhibited limited efficacy in HCC clinical trials. Here, by using HCC cell line models from the Cancer Cell Line Encyclopedia (CCLE) and the Liver Cancer Model Repository (LIMORE), we show that selective FGFR4 inactivation was not sufficient to inhibit cancer cell proliferation and tumor growth in FGF19-positive HCC.
View Article and Find Full Text PDFTwo-dimensional multiferroics, simultaneously harboring antiferromagneticity and ferroelasticity, are essential and highly sought for miniaturized device applications, such as high-density data storage, but thus far they have rarely been explored. Herein, using first principles calculations, we identified two-dimensional antiferromagnetic ferroelasticity in an AgF monolayer that is dynamically and thermally stable, and can be easily fabricated from its bulk. The AgF monolayer is an antiferromagnetic semiconductor with large spin polarization, and with great structural distortion due to its intrinsic Jahn-Teller effect when thinning the AgF down to a monolayer.
View Article and Find Full Text PDFOxygen vacancies are usually thought to be beneficial for photogenerated charge separation. In this work, the oxygen vacancies in ov-Bi O (Bi O with oxygen vacancy) were found to be able to produce O in the dark owing to chemical adsorption. The oxygen vacancies were further found to be responsible for ov-Bi O exhibiting higher O generation under light irradiation with O as the only reactive oxygen species (ROS) than Bi O with O , H O , and others as the ROS.
View Article and Find Full Text PDFTwo-dimensional crystals with coupling of ferroelasticity and attractive electronic properties offer unprecedented opportunities for achieving long-sought controllable devices. However, to date, the reported proposals are mainly based on hypothetical structures. Here, using first-principles calculations, we identify single-layer NbATe (A = Si, Ge), which can be exfoliated from its layered bulk, as a promising candidate.
View Article and Find Full Text PDFValleytronics that relies on the valley degree of freedom is attracting growing interest because it provides a new platform for information storage. One obstacle in this field is to realize valley polarization in an efficient route to manipulate the valley physics. Here we propose a strategy to induce valley polarization by nonmetal atom doping in single-layer TlO.
View Article and Find Full Text PDFTwo-dimensional ferroelastic materials have triggered tremendous interest for applications in nonvolatile memory devices. Here using first-principles calculations, we identify a novel class of two-dimensional ferroelastic materials, single-layer InOY (Y = Cl/Br). The ferroelasticity in single-layer InOY shows a moderate switching barrier and high reversible strain, which are promising for practical applications in nonvolatile memory.
View Article and Find Full Text PDFRibosomal proteins (RPs), the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have additional extra-ribosomal functions, independent of protein biosynthesis, in regulation of diverse cellular processes. Here, we review recent advances in our understanding of how RPs regulate apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, cell migration and invasion, and tumorigenesis through both MDM2/p53-dependent and p53-independent mechanisms.
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