HTLV-1 activates YAP via NF-κB/p65 to promote oncogenesis.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) infection. HTLV-1 exerts its oncogenic functions by interacting with signaling pathways involved in cell proliferation and transformation. Dysregulation of the Hippo/YAP pathway is associated with multiple cancers, including virus-induced malignancies. In the present study, we observe that expression of YAP, which is the key effector of Hippo signaling, is elevated in ATL cells by the action of the HTLV-1 Tax protein. YAP transcriptional activity is remarkably enhanced in HTLV-1-infected cells and ATL patients. In addition, Tax activates the YAP protein via a mechanism involving the NF-κB/p65 pathway. As a mechanism for this cross talk between the Hippo and NF-κB pathways, we found that p65 abrogates the interaction between YAP and LATS1, leading to suppression of YAP phosphorylation, inhibition of ubiquitination-dependent degradation of YAP, and YAP nuclear accumulation. Finally, knockdown of YAP suppresses the proliferation of ATL cells in vitro and tumor formation in ATL-engrafted mice. Taken together, our results suggest that p65-induced YAP activation is essential for ATL pathogenesis and implicate YAP as a potential therapeutic target for ATL treatment.

The SARS-CoV-2 nucleocapsid protein suppresses innate immunity by remodeling stress granules to atypical foci.

Viruses deploy multiple strategies to suppress the host innate immune response to facilitate viral replication and pathogenesis. Typical G3BP1+ stress granules (SGs) are usually formed in host cells after virus infection to restrain viral translation and to stimulate innate immunity. Thus, viruses have evolved various mechanisms to inhibit SGs or to repurpose SG components such as G3BP1. Previous studies showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection inhibited host immunity during the early stage of COVID-19. However, the precise mechanism is not yet well understood. Here we showed that the SARS-CoV-2 nucleocapsid (SARS2-N) protein suppressed the double-stranded RNA (dsRNA)-induced innate immune response, concomitant with inhibition of SGs and the induction of atypical SARS2-N+ /G3BP1+ foci (N+ foci). The SARS2-N protein-induced formation of N+ foci was dependent on the ability of its ITFG motif to hijack G3BP1, which contributed to suppress the innate immune response. Importantly, SARS2-N protein facilitated viral replication by inducing the formation of N+ foci. Viral mutations within SARS2-N protein that impair the formation of N+ foci are associated with the inability of the SARS2-N protein to suppress the immune response. Taken together, our study has revealed a novel mechanism by which SARS-CoV-2 suppresses the innate immune response via induction of atypical N+ foci. We think that this is a critical strategy for viral pathogenesis and has potential therapeutic implications.

The noncanonical role of EZH2 in cancer.

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2). Dysregulation of EZH2 causes alteration of gene expression and functions, thereby promoting cancer development. The regulatory function of EZH2 varies across different tumor types. The canonical role of EZH2 is gene silencing through catalyzing the trimethylation of lysine 27 of histone H3 (H3K27me3) in a PRC2-dependent manner. Accumulating evidence indicates that EZH2 has an H3K27me3-independent function as a transcriptional coactivator and plays a critical role in cancer initiation, development, and progression. In this review, we summarize the regulation and function of EZH2 and focus on the current understanding of the noncanonical role of EZH2 in cancer.

Ultrasensitive photoelectrochemical aptasensor for detecting telomerase activity based on Ag2S/Ag decorated ZnIn2S4/C3N4 3D/2D Z-scheme heterostructures and amplified by Au/Cu2+-boron-nitride nanozyme.

Enzyme-mediated signal amplification strategies have gained substantial attention in photoelectrochemical (PEC) biosensing, while natural enzyme on the photoelectrode inevitably obstructs the interfacial electron transfer, in turn deteriorating the photocurrent responses. Herein, Au nanoparticles and Cu2+-modified boron nitride nanosheets (AuNPs/Cu2+-BNNS) behaved as nanozyme to achieve remarkable magnification in the PEC signals from a novel signal-off aptasensor for ultra-sensitive assay of telomerase (TE) activity based on Ag2S/Ag nanoparticles decorated ZnIn2S4/C3N4 Z-scheme heterostructures (termed as Ag2S/Ag/ZnIn2S4/C3N4, synthesized by hydrothermal treatment). Specifically, telomerase primer sequences (TS) were extended by TE in the presence of deoxyribonucleoside triphosphates (dNTPs), which was directly bond with the thiol modified complementary DNA (cDNA), achieving efficient linkage with the nanozyme via Au-S bond. The immobilized nanoenzyme catalyzed the oxidation between 4-chloro-1-naphthol (4-CN) and H2O2 to generate insoluble precipitation on the photo-electrode. By virtue of the inhibited PEC signals with the TE-enabled TS extension, an aptasensor for assay of TE activity was developed, showing the wide linear range of 50-5×105 cell mL-1 and a low detection limit of 19 cell mL-1. This work provides some valuable guidelines for developing advanced nanozyme-based PEC bioanalysis of diverse cancer cells.