典型文献
Atypical chemokine receptor 3 induces colorectal tumorigenesis in mice by promoting β-arrestin-NOLC1-fibrillarin-dependent rRNA biogenesis
文献摘要：
Atypical chemokine receptor 3(ACKR3)has emerged as a key player in various biological processes.Its atypical"intercepting receptor"properties have established ACKR3 as the major regulator in the pathophysiological processes in many diseases.In this study,we investigated the role of ACKR3 activation in promoting colorectal tumorigenesis.We showed that ACKR3 expression levels were significantly increased in human colon cancer tissues,and high levels of ACKR3 predicted the increased severity of cancer.In Villin-ACKR3 transgenic mice with a high expression level of CKR3 in their intestinal epithelial cells,administration of AOM/DSS induced more severe colorectal tumorigenesis than their WT littermates.Cancer cells of Villin-ACKR3 transgenic mice were characterised by the nuclear β-arrestin-1(β-arr1)-activated perturbation of rRNA biogenesis.In HCT116 cells,cotreatment with CXCL12 and AMD3100 selectively activated ACKR3 and induced nuclear translocation of β-arr1,leading to an interaction of β-arr1 with nucleolar and coiled-body phosphoprotein 1(NOLC1).NOLC1,as the phosphorylated protein,further interacted with fibrilllarin,a conserved nucleolar methyltransferase responsible for ribosomal RNA methylation in the nucleolus,thereby increasing the methylation in histone H2A and promoting rRNA transcription in ribosome biogenesis.In conclusion,ACKR3 promotes colorectal tumorigenesis through the perturbation of rRNA biogenesis by the β-arrl-induced interaction of NOLC1 with fibrillarin.
文献关键词：
中图分类号：
作者姓名：
Juan Yang;Rong-rong Miao;Ya-nan Li;Ting Pan;Shu-hua Wu;Xian-jun Qu;Shu-xiang Cui
作者机构：
Beijing Key Laboratory of Environmental Toxicology,Department of Toxicology and Sanitary Chemistry,School of Public Health,Capital Medical University,Beijing 100069,China;Department of Comprehensive Ward,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China;Department of Pharmacology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China;Department of Pathology,Hospital of Bin Zhou Medical College,Binzhou 256603,China
文献出处：
引用格式：
[1]Juan Yang;Rong-rong Miao;Ya-nan Li;Ting Pan;Shu-hua Wu;Xian-jun Qu;Shu-xiang Cui-.Atypical chemokine receptor 3 induces colorectal tumorigenesis in mice by promoting β-arrestin-NOLC1-fibrillarin-dependent rRNA biogenesis)[J].中国药理学报（英文版）,2022(11):2967-2976
A类：
NOLC1,fibrillarin,ACKR3,CKR3,littermates,arr1,cotreatment,fibrilllarin,nucleolus,arrl
B类：
Atypical,chemokine,receptor,induces,colorectal,tumorigenesis,mice,promoting,arrestin,dependent,rRNA,biogenesis,has,emerged,key,player,various,biological,processes,Its,atypical,intercepting,properties,have,established,major,regulator,pathophysiological,many,diseases,In,this,study,investigated,role,activation,We,showed,that,expression,levels,were,significantly,increased,human,colon,cancer,tissues,high,predicted,severity,Villin,transgenic,their,intestinal,epithelial,cells,administration,AOM,DSS,induced,more,severe,than,WT,Cancer,characterised,nuclear,activated,perturbation,HCT116,CXCL12,AMD3100,selectively,translocation,leading,interaction,nucleolar,coiled,body,phosphoprotein,phosphorylated,further,interacted,conserved,methyltransferase,responsible,ribosomal,methylation,thereby,increasing,histone,H2A,transcription,ribosome,conclusion,promotes,through
AB值：
0.459853
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