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Julhash U. Kazi Rohit A. Chougule Tianfeng Li Xianwei Su Sausan A. Moharram Kaja Rupar Alissa Marhäll Mohiuddin Gazi Jianmin Sun Hui Zhao Lars Rönnstrand 《Cellular and molecular life sciences : CMLS》2017,74(14):2679-2688
The type III receptor tyrosine kinase FLT3 is frequently mutated in acute myeloid leukemia. Oncogenic FLT3 mutants display constitutive activity leading to aberrant cell proliferation and survival. Phosphorylation on several critical tyrosine residues is known to be essential for FLT3 signaling. Among these tyrosine residues, Y842 is located in the so-called activation loop. The position of this tyrosine residue is well conserved in all receptor tyrosine kinases. It has been reported that phosphorylation of the activation loop tyrosine is critical for catalytic activity for some but not all receptor tyrosine kinases. The role of Y842 residue in FLT3 signaling has not yet been studied. In this report, we show that Y842 is not important for FLT3 activation or ubiquitination but plays a critical role in regulating signaling downstream of the receptor as well as controlling receptor stability. We found that mutation of Y842 in the FLT3-ITD oncogenic mutant background reduced cell viability and increased apoptosis. Furthermore, the introduction of the Y842 mutation in the FLT3-ITD background led to a dramatic reduction in in vitro colony forming capacity. Additionally, mice injected with cells expressing FLT3-ITD/Y842F displayed a significant delay in tumor formation, compared to FLT3-ITD expressing cells. Microarray analysis comparing gene expression regulated by FLT3-ITD versus FLT3-ITD/Y842F demonstrated that mutation of Y842 causes suppression of anti-apoptotic genes. Furthermore, we showed that cells expressing FLT3-ITD/Y842F display impaired activity of the RAS/ERK pathway due to reduced interaction between FLT3 and SHP2 leading to reduced SHP2 activation. Thus, we suggest that Y842 is critical for FLT3-mediated RAS/ERK signaling and cellular transformation. 相似文献
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Duyilemi C. Ajonijebu Oualid Abboussi Vivienne A. Russell Musa V. Mabandla William M. U. Daniels 《Cellular and molecular life sciences : CMLS》2017,74(15):2735-2747
The detrimental effects of drug abuse are apparently not limited to individuals but may also impact the vulnerability of their progenies to develop addictive behaviours. Epigenetic signatures, early life experience and environmental factors, converge to influence gene expression patterns in addiction phenotypes and consequently may serve as mediators of behavioural trait transmission between generations. The majority of studies investigating the role of epigenetics in addiction do not consider the influence of social interactions. This shortcoming in current experimental approaches necessitates developing social models that reflect the addictive behaviour in a free-living social environment. Furthermore, this review also reports on the advancement of interventions for drug addiction and takes into account the emerging roles of histone deacetylase (HDAC) inhibitors in the etiology of drug addiction and that HDAC may be a potential therapeutic target at nucleosomal level to improve treatment outcomes. 相似文献
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Mirco Castoldi Martina U. Muckenthaler 《Cellular and molecular life sciences : CMLS》2012,69(23):3945-3952
Iron homeostasis is maintained at the cellular and systemic levels to assure adequate iron supply while preventing iron overload. The identification of genes mutated in patients with iron-related disorders or animal models with imbalances of iron homeostasis gave insight into the molecular mechanisms underlying processes critical for balancing iron levels, such as iron uptake, storage, export, and monitoring of available iron. MicroRNAs control genes involved in some of these processes adding an additional level of complexity to the regulation of iron metabolism. This review summarizes recent advances how miRNAs regulate iron homeostasis. 相似文献
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Lifestyle transitions in plant pathogenic Colletotrichum fungi deciphered by genome and transcriptome analyses 总被引:8,自引:0,他引:8
RJ O'Connell MR Thon S Hacquard SG Amyotte J Kleemann MF Torres U Damm EA Buiate L Epstein N Alkan J Altmüller L Alvarado-Balderrama CA Bauser C Becker BW Birren Z Chen J Choi JA Crouch JP Duvick MA Farman P Gan D Heiman B Henrissat RJ Howard M Kabbage C Koch B Kracher Y Kubo AD Law MH Lebrun YH Lee I Miyara N Moore U Neumann K Nordström DG Panaccione R Panstruga M Place RH Proctor D Prusky G Rech R Reinhardt JA Rollins S Rounsley CL Schardl DC Schwartz N Shenoy K Shirasu UR Sikhakolli K Stüber 《Nature genetics》2012,44(9):1060-1065
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周跃花 《西安联合大学学报》1999,(2)
通过工艺计算,定量分析比较 S O2 转化中“ⅢⅠ- ⅣⅡ”和“ⅢⅡ- ⅣⅠ”两种换热流程的差异,论证了就换热情况而言,“ⅢⅠ- ⅣⅡ”流程优于“ⅢⅡ- ⅣⅠ”流程 相似文献
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用柱层析和TLC分离小麦PGIP和植保素 总被引:1,自引:0,他引:1
植物抗病能力大小的测定需要比较准确可靠且相对简便的办法。采用接种病菌于植物上观察染菌情况虽然直观,但受病菌本身的生理状态及外界环境影响很大,且不便于定量的表述。因此,选择合适的生理生化指标作为植物抗性大小的衡量标准,对于植物病理的研究具有重要的意义。选择了小麦体系的两种抗性物质- 小麦植保素和 P G I P作为小麦的抗性指标来分离分析 相似文献