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941.
Monika Jain Bagher Golzarroshan ChiaLiang Lin Sashank Agrawal WeiHsuan Tang ChiuJu Wu Hanna S. Yuan 《Protein science : a publication of the Protein Society》2022,31(5)
Human Suv3 is a unique homodimeric helicase that constitutes the major component of the mitochondrial degradosome to work cooperatively with exoribonuclease PNPase for efficient RNA decay. However, the molecular mechanism of how Suv3 is assembled into a homodimer to unwind RNA remains elusive. Here, we show that dimeric Suv3 preferentially binds to and unwinds DNA–DNA, DNA–RNA, and RNA–RNA duplexes with a long 3′ overhang (≥10 nucleotides). The C‐terminal tail (CTT)‐truncated Suv3 (Suv3ΔC) becomes a monomeric protein that binds to and unwinds duplex substrates with ~six to sevenfold lower activities relative to dimeric Suv3. Only dimeric Suv3, but not monomeric Suv3ΔC, binds RNA independently of ATP or ADP, and is capable of interacting with PNPase, indicating that dimeric Suv3 assembly ensures its continuous association with RNA and PNPase during ATP hydrolysis cycles for efficient RNA degradation. We further determined the crystal structure of the apo‐form of Suv3ΔC, and SAXS structures of dimeric Suv3 and PNPase–Suv3 complex, showing that dimeric Suv3 caps on the top of PNPase via interactions with S1 domains, and forms a dumbbell‐shaped degradosome complex with PNPase. Overall, this study reveals that Suv3 is assembled into a dimeric helicase by its CTT for efficient and persistent RNA binding and unwinding to facilitate interactions with PNPase, promote RNA degradation, and maintain mitochondrial genome integrity and homeostasis. 相似文献
942.
943.
944.
Tengfeng Yan Yinqiu Tan Gang Deng Zhiqiang Sun Baohui Liu Yixuan Wang Fanen Yuan Qian Sun Ping Hu Lun Gao Daofeng Tian Qianxue Chen 《Cell death & disease》2022,13(4)
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. The unregulated expression of Claudin-4 (CLDN4) plays an important role in tumor progression. However, the biological role of CLDN4 in GBM is still unknown. This study aimed to determine whether CLDN4 mediates glioma malignant progression, if so, it would further explore the molecular mechanisms of carcinogenesis. Our results revealed that CLDN4 was significantly upregulated in glioma specimens and cells. The inhibition of CLND4 expression could inhibit mesenchymal transformation, cell invasion, cell migration and tumor growth in vitro and in vivo. Moreover, combined with in vitro analysis, we found that CLDN4 can modulate tumor necrosis factor-α (TNF-α) signal pathway. Meanwhile, we also validated that the transforming growth factor-β (TGF-β) signal pathway can upregulate the expression of CLDN4, and promote the invasion ability of GBM cells. Conversely, TGF-β signal pathway inhibitor ITD-1 can downregulate the expression of CLDN4, and inhibit the invasion ability of GBM cells. Furthermore, we found that TGF-β can promote the nuclear translocation of CLDN4. In summary, our findings indicated that the TGF-β/CLDN4/TNF-α/NF-κB signal axis plays a key role in the biological progression of glioma. Disrupting the function of this signal axis may represent a new treatment strategy for patients with GBM.Subject terms: CNS cancer, Epithelial-mesenchymal transition 相似文献
945.
Guangwen Wang Yuhui Zhao Yuan Zhou Li Jiang Libin Liang Fandi Kong Ya Yan Xuyuan Wang Yihan Wang Xia Wen Xianying Zeng Guobin Tian Guohua Deng Jianzhong Shi Liling Liu Hualan Chen Chengjun Li 《PLoS pathogens》2022,18(4)
Host defense systems employ posttranslational modifications to protect against invading pathogens. Here, we found that protein inhibitor of activated STAT 1 (PIAS1) interacts with the nucleoprotein (NP), polymerase basic protein 1 (PB1), and polymerase basic protein 2 (PB2) of influenza A virus (IAV). Lentiviral-mediated stable overexpression of PIAS1 dramatically suppressed the replication of IAV, whereas siRNA knockdown or CRISPR/Cas9 knockout of PIAS1 expression significantly increased virus growth. The expression of PIAS1 was significantly induced upon IAV infection in both cell culture and mice, and PIAS1 was involved in the overall increase in cellular SUMOylation induced by IAV infection. We found that PIAS1 inhibited the activity of the viral RNP complex, whereas the C351S or W372A mutant of PIAS1, which lacks the SUMO E3 ligase activity, lost the ability to suppress the activity of the viral RNP complex. Notably, the SUMO E3 ligase activity of PIAS1 catalyzed robust SUMOylation of PB2, but had no role in PB1 SUMOylation and a minimal role in NP SUMOylation. Moreover, PIAS1-mediated SUMOylation remarkably reduced the stability of IAV PB2. When tested in vivo, we found that the downregulation of Pias1 expression in mice enhanced the growth and virulence of IAV. Together, our findings define PIAS1 as a restriction factor for the replication and pathogenesis of IAV. 相似文献
946.
Xiaoyan Hao Yuan Guo Rui Wang Xueyuan Yu Lin He Maoguo Shu 《Acta biochimica et biophysica Sinica》2021,(4):501-510
The rate of fat graft survival is a critical aspect of successful surgery and has been a matter of concern for over 20 years.Owing to their anti-inflammatory ef... 相似文献
947.
Dekai Yuan Ping Wang Liju Yang Jesse L Quimby Ya-Ping Sun 《Experimental biology and medicine (Maywood, N.J.)》2022,247(4):300
Carbon “quantum” dots or carbon dots (CDots) exploit and enhance the intrinsic photoexcited state properties and processes of small carbon nanoparticles via effective nanoparticle surface passivation by chemical functionalization with organic species. The optical properties and photoinduced redox characteristics of CDots are competitive to those of established conventional semiconductor quantum dots and also fullerenes and other carbon nanomaterials. Highlighted here are major advances in the exploration of CDots for their serving as high-performance yet nontoxic fluorescence probes for one- and multi-photon bioimaging in vitro and in vivo, and for their uniquely potent antimicrobial function to inactivate effectively and efficiently some of the toughest bacterial pathogens and viruses under visible/natural or ambient light conditions. Opportunities and challenges in the further development of the CDots platform and related technologies are discussed. 相似文献
948.
949.
Fu-Chen Song Jia-Qin Yuan Mei-Dong Zhu Qi Li Sheng-Hua Liu Lei Zhang Cheng Zhao 《Bioscience reports》2022,42(3)
Diabetic foot ulcer (DFU) is a kind of common and disabling complication of Diabetes Mellitus (DM). Emerging studies have demonstrated that tendon fibroblasts play a crucial role in remodeling phase of wound healing. However, little is known about the mechanism underlying high glucose (HG)-induced decrease in tendon fibroblasts viability. In the present study, the rat models of DFU were established, and collagen deposition, autophagy activation and cell apoptosis in tendon tissues were assessed using Hematoxylin–Eosin (HE) staining, immunohistochemistry (IHC), and TdT-mediated dUTP Nick-End Labeling (TUNEL) assay, respectively. Tendon fibroblasts were isolated from Achilles tendon of the both limbs, and the effect of HG on autophagy activation in tendon fibroblasts was assessed using Western blot analysis, Cell Counting Kit-8 (CCK-8) assay, and flow cytometry. We found that cell apoptosis was increased significantly and autophagy activation was decreased in foot tendon tissues of DFU rats compared with normal tissues. The role of HG in regulating tendon fibroblasts viability was then investigated in vitro, and data showed that HG repressed cell viability and increased cell apoptosis. Furthermore, HG treatment reduced LC3-II expression and increased p62 expression, indicating that HG repressed autophagy activation of tendon fibroblasts. The autophagy activator rapamycin reversed the effect. More importantly, rapamycin alleviated the suppressive role of HG in tendon fibroblasts viability. Taken together, our data demonstrate that HG represses tendon fibroblasts proliferation by inhibiting autophagy activation in tendon injury. 相似文献
950.