Atypical chemokine receptor 3 induces colorectal tumorigenesis in mice by promoting β-arrestin-NOLC1-fibrillarin-dependent rRNA biogenesis
Atypical chemokine receptor 3 induces colorectal tumorigenesis in mice by promoting β-arrestin-NOLC1-fibrillarin-dependent rRNA biogenesis
复制标题
非典型趋化因子受体 3 通过促进 β-arrestin-NOLC1-fibrillarin 依赖性 rRNA 生物发生诱导小鼠结直肠肿瘤发生
DOI：
10.1038/s41401-022-00901-x
复制
发表时间：
2022-04
影响因子：
8.2
通讯作者：
Shu-xiang Cui
中科院分区：
文献类型：
--
作者：
Juan Yang;Rong-rong Miao;Ya-nan Li;Ting Pan;Shu-hua Wu;Xian-jun Qu;Shu-xiang Cui
非典型趋化因子受体3（ACKR 3）已成为各种生物过程中的关键参与者。其非典型的“拦截受体”性质已经确立了ACKR 3作为许多疾病的病理生理过程中的主要调节剂。在这项研究中，我们研究了ACKR 3激活在促进结直肠肿瘤发生中的作用。我们发现，人类结肠癌组织中的ACKR 3表达水平显著增加，高水平的ACKR 3预测癌症严重程度的增加。在肠上皮细胞中CKR 3表达水平较高的Villin-ACKR 3转基因小鼠中，给予AOM/DSS诱导了比WT同窝小鼠更严重的结直肠肿瘤发生。Villin-ACKR 3转基因小鼠的癌细胞的特征在于细胞核β-arrestin-1（β-arr 1）激活的rRNA生物发生扰动。在HCT 116细胞中，CXCL 12和AMD 3100共处理选择性激活了ACKR 3并诱导β-arr 1核转位，导致β-arr 1与核仁和卷曲体磷蛋白1（NOLC 1）相互作用。NOLC 1作为磷酸化的蛋白质，进一步与一种保守的核仁甲基转移酶fibrillarin相互作用，从而增加组蛋白H2 A的甲基化，促进核糖体生物合成中rRNA的转录。总之，ACKR 3通过β-arr 1诱导的NOLC 1与原纤维蛋白的相互作用干扰rRNA生物合成来促进结直肠肿瘤发生。
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 fibrillarin, 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-arr1-induced interaction of NOLC1 with fibrillarin.
登录
查看更多内容
影响因子：
5.8
作者：
Bryant CJ;McCool MA;Abriola L;Surovtseva YV;Baserga SJ
通讯作者：
Baserga SJ
影响因子：
3.9
作者：
Cancellieri, Cinzia;Vacchini, Alessandro;Borroni, Elena M.
通讯作者：
Borroni, Elena M.
DOI：
10.1074/jbc.m208109200
发表时间：
2003-03
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
Ping Wang;Yalan Wu;X. Ge;Lan Ma;G. Pei
通讯作者：
Ping Wang;Yalan Wu;X. Ge;Lan Ma;G. Pei
DOI：
10.1016/s0021-9258(19)84375-2
发表时间：
1996-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
U. Meier
通讯作者：
U. Meier
影响因子：
8
作者：
Luker, K. E.;Lewin, S. A.;Mihalko, L. A.;Schmidt, B. T.;Winkler, J. S.;Coggins, N. L.;Thomas, D. G.;Luker, G. D.
通讯作者：
Luker, G. D.