Zhou, Qingxin; Lin, Meihua; Feng, Xing; Ma, Fei; Zhu, Yuekun; Liu, Xing; Qu, Chao; Sui, Hong; Sun, Bei; Zhu, Anlong; Zhang, Heng; Huang, He; Gao, Zhi; Zhao, Yongxiang; Sun, Jiangyun; Bai, Yuxian; Jin, Junfei; Hong, Xuehui; Zou, Chang; Zhang, Zhiyong published the artcile< Targeting CLK3 inhibits the progression of cholangiocarcinoma by reprogramming nucleotide metabolism>, Related Products of 6055-19-2, the main research area is cholangiocarcinoma CLK3 serine threonine tyrosine nucleotide metabolism.
CDC-like kinase 3 (CLK3) is a dual specificity kinase that functions on substrates containing serine/threonine and tyrosine. But its role in human cancer remains unknown. Herein, we demonstrated that CLK3 was significantly up-regulated in cholangiocarcinoma (CCA) and identified a recurrent Q607R somatic substitution that represented a gain-of-function mutation in the CLK3 kinase domain. Gene ontol. term enrichment suggested that high CLK3 expression in CCA patients mainly was associated with nucleotide metabolism reprogramming, which was further confirmed by comparing metabolic profiling of CCA cells. CLK3 directly phosphorylated USP13 at Y708, which promoted its binding to c-Myc, thereby preventing Fbxl14-mediated c-Myc ubiquitination and activating the transcription of purine metabolic genes. Notably, the CCA-associated CLK3-Q607R mutant induced USP13-Y708 phosphorylation and enhanced the activity of c-Myc. In turn, c-Myc transcriptionally up-regulated CLK3. Finally, we identified tacrine hydrochloride as a potential drug to inhibit aberrant CLK3-induced CCA. These findings demonstrate that CLK3 plays a crucial role in CCA purine metabolism, suggesting a potential therapeutic utility.
Journal of Experimental Medicine published new progress about Cell infiltration. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Related Products of 6055-19-2.
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Chlorides – an overview | ScienceDirect Topics