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Mei-yi Pu Anwarul A. Akhand Masashi Kato Teruhiko Koike Michinari Hamaguchi Haruhiko Suzuki Izumi Nakashima 《Journal of cellular biochemistry》1996,63(1):104-114
Little is known about the regulatory mechanism of c-Src kinase in cells except the suggested regulation through phosphorylation and dephosphorylation of its carboxyl terminal tyrosine residue (Y527). We here demonstrated that exposure of NIH3T3 cells to mercuric chloride (HgCl2) induces both aggregation and activation of Src kinase protein through a redox-linked mechanism. The aggregation of Src proteins was suggested to be induced by the sulfhydryl groups-to-Hg2+ reaction-mediated polymerization of cell membrane proteins to which the Src proteins associate noncovalently. The possibility was ruled out that the aggregation occurred secondarily to the promotion of protein tyrosine phosphorylation. Further study revealed that the Src kinase was activated by HgCl2 at least in part independent of the known Csk kinase-linked or Y527-phosphorylation/dephosphorylation-mediated control. Correspondingly, CNBr cleavage mapping of phosphopeptides for autophosphorylated c-Src protein demonstrated selective promotion of phosphorylation at Y416 in HgCl2-treated cells without obvious change in the phosphorylation level at Y527. These results suggest a unique protein sulfhydryl modification-based pathway of signal transduction for activating Src kinase in NIH3T3 cells. © 1996 Wiley-Liss, Inc. 相似文献
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Zhongyi Fan Jingjing Duan Pu Luo Ling Shao Qiong Chen Xiaohua Tan Lei Zhang Xiaojie Xu 《Cell death & disease》2022,13(4)
Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.Subject terms: GSE22138Eye cancer, Prognostic markers 相似文献
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Lin Peng Min Zhao Tianqi Liu Jiangbo Chen Pin Gao Lei Chen Pu Xing Zaozao Wang Jiabo Di Qiang Xu Hong Qu Beihai Jiang Xiangqian Su 《Cell death & disease》2022,13(4)
Genomic instability plays a key role in the initiation and progression of colorectal cancer (CRC). Although cancer driver genes in CRC have been well characterized, identifying novel genes associated with carcinogenesis and treatment remains challenging because of tumor heterogeneity. Here, we analyzed the genomic alterations of 45 samples from CRC patients in northern China by whole-exome sequencing. In addition to the identification of six well-known CRC driver genes (APC, TP53, KRAS, FBXW7, PIK3CA, and PABPC), two tumor-related genes (MTCH2 and HSPA6) were detected, along with RRP7A and GXYLT1, which have not been previously linked to cancer. GXYLT1 was mutated in 40% (18/45) of the samples in our cohort. Functionally, GXYLT1 promoted migration and invasion in vitro and metastasis in vivo, while the GXYLT1S212* mutant induced significantly greater effect. Furthermore, both GXYLT1 and GXYLT1S212* interacted with ERK2. GXYLT1 induced metastasis via a mechanism involving the Notch and MAPK pathways, whereas the GXYLT1S212* mutant mainly promoted metastasis by activating the MAPK pathway. We propose that GXYLT1 acts as a novel metastasis-associated driver gene and GXYLT1S212* might serve as a potential indicator for therapies targeting the MAPK pathway in CRC.Subject terms: Cancer genomics, Colorectal cancer, Metastasis, Oncogenes, Cell signalling 相似文献
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Lu Qiao Lili Men Shanshan Yu Junjie Yao Yu Li Mingming Wang Ying Yu Ning Wang Liyuan Ran Yingjie Wu Jianling Du 《Cell death & disease》2022,13(3)
Nonalcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), which are all complex metabolic disorders. Selenoprotein S (SelS) is an endoplasmic reticulum (ER) resident selenoprotein involved in regulating ER stress and has been found to participate in the occurrence and development of IR and T2DM. However, the potential role and mechanism of SelS in NAFLD remains unclear. Here, we analyzed SelS expression in the liver of high-fat diet (HFD)-fed mice and obese T2DM model (db/db) mice and generated hepatocyte-specific SelS knockout (SelSH-KO) mice using the Cre-loxP system. We showed that hepatic SelS expression levels were significantly downregulated in HFD-fed mice and db/db mice. Hepatic SelS deficiency markedly increased ER stress markers in the liver and caused hepatic steatosis via increased fatty acid uptake and reduced fatty acid oxidation. Impaired insulin signaling was detected in the liver of SelSH-KO mice with decreased phosphorylation levels of insulin receptor substrate 1 (IRS1) and protein kinase B (PKB/Akt), which ultimately led to disturbed glucose homeostasis. Meanwhile, our results showed hepatic protein kinase Cɛ (PKCɛ) activation participated in the negative regulation of insulin signaling in SelSH-KO mice. Moreover, the inhibitory effect of SelS on hepatic steatosis and IR was confirmed by SelS overexpression in primary hepatocytes in vitro. Thus, we conclude that hepatic SelS plays a key role in regulating hepatic lipid accumulation and insulin action, suggesting that SelS may be a potential intervention target for the prevention and treatment of NAFLD and T2DM.Subject terms: Metabolic syndrome, Obesity 相似文献
47.
研究与HIV 1感染相关的基质细胞衍生因子 (SDF1)等位基因突变频率和多态性在中国 4个少数民族的分布特征。应用PCR/ RFLP等方法检测回族 (5 7例 )、鄂伦春族 (71例 )、蒙古族 (30例 )及锡伯族 (2 6例 )共 184个个体中SDF1 -3’A基因突变频率。结果得出中国 4个民族中SDF1- 3’A基因的基因频率分别为 :蒙古族为 38 3%,锡伯族为 2 3 .1%,回族为 2 0 .2 %,鄂伦春族为 10 .6 %。中国 4个少数民族中SDF1- 3’A等位基因频率存在较大的差异 (χ2 =37 .82 6 ,P<0.01) , 提示这 4 个民族的遗传结构存在着一定的差异。 本研究 为评估中国不同民族对 HIV-1 的易感性及艾滋病的流行病学研究提供了基本数据。 相似文献
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Immunohistochemical and in situ hybridization studies of gonadotropin releasing hormone (GnRH) and its receptor in rat digestive tract 总被引:23,自引:0,他引:23
GnRH(LH-RH) is first discovered in the hypothalamus and found to have a role in regulation of reproduction. With the study on it deepening, GnRH was demonnstrated that it also exists in a number of organs beyond the hypothalamus and acts on extrapituitary organs. To study whether digestive tract synthesizes GnRH and its receptor and, if it does, by what cells. In the experiment, the locallizations of GnRH and its receptors in rat digestive tract were studied using immunohistochemistry and in situ hybridization. The parietal cells of gastric gland, the villous and glandular epithelium in small and large intestine and parasympathetic ganglion cells of myenteric plexus showed GnRH immunoreactivity; GnRH mRNA hybridization signal was detected. The epithelium of gastric pit and the cells above in digestive tract showed GnRH receptor immunoreactivity; GnRH receptor mRNA hybridization signal was detected. The immunoreactive and signal materials distributed in cytoplasm of all positive cells, with nuclei being immunonegative and with no hybridization signal. These results suggested that the digestive tract can produce GnRH and express GnRH receptor; GnRH may also be a gastrointestinal hormone. 相似文献