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71.
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Yinzhu Hou Tieliang Gan Tiantian Fang Yao Zhao Qun Luo Xingkai Liu Luyu Qi Yanyan Zhang Feifei Jia Juanjuan Han Shumu Li Shijun Wang Fuyi Wang 《Nucleic acids research》2022,50(6):3070
Pyridostatin (PDS) is a well-known G-quadruplex (G4) inducer and stabilizer, yet its target genes have remained unclear. Herein, applying MS proteomics strategy, we revealed PDS significantly downregulated 22 proteins but upregulated 16 proteins in HeLa cancer cells, of which the genes both contain a number of G4 potential sequences, implying that PDS regulation on gene expression is far more complicated than inducing/stabilizing G4 structures. The PDS-downregulated proteins consequently upregulated 6 proteins to activate cyclin and cell cycle regulation, suggesting that PDS itself is not a potential anticancer agent, at least toward HeLa cancer cells. Importantly, SUB1, which encodes human positive cofactor and DNA lesion sensor PC4, was downregulated by 4.76-fold. Further studies demonstrated that the downregulation of PC4 dramatically promoted the cytotoxicity of trans-[PtCl2(NH3)(thiazole)] (trans-PtTz) toward HeLa cells to a similar level of cisplatin, contributable to retarding the repair of 1,3-trans-PtTz crosslinked DNA lesion mediated by PC4. These findings not only provide new insights into better understanding on the biological functions of PDS but also implicate a strategy for the rational design of novel multi-targeting platinum anticancer drugs via conjugation of PDS as a ligand to the coordination scaffold of transplatin for battling drug resistance to cisplatin. 相似文献
73.
Shuangze Han Ruike Wang Yangnan Zhang Xiaoying Li Yu Gan Feng Gao Pengfei Rong Wei Wang Wei Li 《International journal of biological sciences》2022,18(6):2292
Ubiquitination is vital for multiple cellular processes via dynamic modulation of proteins related to cell growth, proliferation, and survival. Of the ubiquitination system components, E3 ubiquitin ligases and deubiquitinases have the most prominent roles in modulating tumor metastasis. This review will briefly summarize the observations and underlying mechanisms of multiple E3 ubiquitin ligases and deubiquitinases to regulate tumor metastasis. Further, we will discuss the relationship and importance between ubiquitination components and tumor progression. 相似文献
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75.
XiaoYan Zhou ChangJiang Ying Bin Hu YuSheng Zhang Tian Gan YanDong Zhu Nan Wang AnAn Li YuanJian Song 《Aging cell》2022,21(2)
In this study, we explored the precise mechanisms underlying the receptor for advanced glycation end products (RAGE)‐mediated neuronal loss and behavioral dysfunction induced by hyperglycemia. We used immunoprecipitation (IP) and GST pull‐down assays to assess the interaction between RAGE and mitogen‐activated protein kinase kinase 3 (MKK3). Then, we investigated the effect of specific mutation of RAGE on plasticity at hippocampal synapses and behavioral deficits in db/db mice through electrophysiological recordings, morphological assays, and behavioral tests. We discovered that RAGE binds MKK3 and that this binding is required for assembly of the MEKK3‐MKK3‐p38 signaling module. Mechanistically, we found that activation of p38 mitogen‐activated protein kinase (MAPK)/NF‐κB signaling depends on mediation of the RAGE‐MKK3 interaction by C‐terminal RAGE (ctRAGE) amino acids (AAs) 2‐5. We found that ctRAGE R2A‐K3A‐R4A‐Q5A mutation suppressed neuronal damage, improved synaptic plasticity, and alleviated behavioral deficits in diabetic mice by disrupting the RAGE‐MKK3 conjugation. High glucose induces direct binding of RAGE and MKK3 via ctRAGE AAs 2‐5, which leads to assembly of the MEKK3‐MKK3‐p38 signaling module and subsequent activation of the p38MAPK/NF‐κB pathway, and ultimately results in diabetic encephalopathy (DE). 相似文献
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Ching-Lee?Wong Sook-Yee?Gan Siew-Moi?PhangEmail author 《Journal of applied phycology》2004,16(6):439-445
Two Sargassum species (S. baccularia and S. polycystum) collected from Teluk Kemang and Cape Rachado, Port Dickson, Negeri Sembilan, Malaysia, which are alike in morphology except for the rhizoidal system and vesicles, were characterised using random amplified polymorphism DNA (RAPD). The genomic DNA of both species was isolated from the leaves using a modified CTAB method. Four random primers, that is, OPA2, OPA3, OPA4 and OPA13, successfully amplified the DNA. The polymorphisms generated by these four primers were analysed using the Dice Coefficient of Similarity and cluster analysis was carried out using GelCompar II Version 2.0 (Applied Maths, Kortrijk, Belgium) based on UPGMA. DNA analysis showed that three primers were able to differentiate the two species. Morphological analysis using Principal Components Analysis (PCA) and discriminant function analysis supported the molecular data. Both species are characterised by heavily muricate main branches, oblong-lanceolate leaves with dentate margins and discoid holdfasts and spherical vesicles; both are dioecious. The only difference is that S. polycystum has secondary holdfasts transformed into stolons. This last characteristic is therefore a very important criterion and may contribute to the difference shown by DNA analysis. 相似文献
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80.
ErbB-2/HER2 is an oncogenic tyrosine kinase that regulates a signalling network by forming ligand-induced heterodimers with several growth factor receptors of the ErbB family. Hsp90 and co-chaperones regulate degradation of ErbB-2 but not other ErbB members. Here, we report that the role of Hsp90 in modulating the ErbB network extends beyond regulation of protein stability. The capacity of ErbB-2 to recruit ligand-bound receptors into active heterodimers is limited by Hsp90, which is dissociated from ErbB-2 following ligand-induced heterodimerization. We show that Hsp90 binds a specific loop within the kinase domain of ErbB-2, thereby restraining heterodimer formation and catalytic function. These results define a role for Hsp90 as a molecular switch regulating the ErbB signalling network by limiting formation of ErbB-2-centred receptor complexes. 相似文献