Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers.,Nature Communications

当前位置： X-MOL 学术 › Nat. Commun. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers.
Nature Communications ( IF 14.7 ) Pub Date : 2016-11-18 , DOI: 10.1038/ncomms13418
Eva Pérez-Guijarro ₁ , Panagiotis Karras ₁ , Metehan Cifdaloz ₁ , Raúl Martínez-Herranz ₁ , Estela Cañón ₁ , Osvaldo Graña ₂ , Celia Horcajada-Reales ₃ , Direna Alonso-Curbelo ₁ , Tonantzin G Calvo ₁ , Gonzalo Gómez-López ₂ , Nicolas Bellora ₄ , Erica Riveiro-Falkenbach ₅ , Pablo L Ortiz-Romero ₅ , José L Rodríguez-Peralto ₅ , Lorena Maestre ₆ , Giovanna Roncador ₆ , Juan C de Agustín Asensio ₇ , Colin R Goding ₈ , Eduardo Eyras _{4,

9} , Diego Megías ₁₀ , Raúl Méndez _{9,

11} , María S Soengas ₁

Affiliation

Melanoma Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
Bioinformatics Unit (CNIO), Madrid 28029, Spain.
Department of Dermatology, Hospital Gregorio Marañón, Madrid 28003, Spain.
Department of Experimental and Health Sciences, Universidad Pompeu Fabra, Barcelona 08002, Spain.
Instituto de Investigación i+12, Hospital 12 de Octubre, Medical School, Universidad Complutense, Madrid 28041, Spain.
Monoclonal Antibodies Unit, Biotechnology Programme (CNIO), Madrid 28029, Spain.
Department of Pediatric Surgery, Hospital Gregorio Marañón, Madrid 28003, Spain.
Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, Spain.
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain.
Confocal Microscopy Unit, (CNIO) Madrid 28029, Spain.
Translational Control of Cell Cycle and Differentiation Group, Molecular Medicine Department, Institute for Research in Biomedicine (IRB), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.

Nuclear 3'-end-polyadenylation is essential for the transport, stability and translation of virtually all eukaryotic mRNAs. Poly(A) tail extension can also occur in the cytoplasm, but the transcripts involved are incompletely understood, particularly in cancer. Here we identify a lineage-specific requirement of the cytoplasmic polyadenylation binding protein 4 (CPEB4) in malignant melanoma. CPEB4 is upregulated early in melanoma progression, as defined by computational and histological analyses. Melanoma cells are distinct from other tumour cell types in their dependency on CPEB4, not only to prevent mitotic aberrations, but to progress through G1/S cell cycle checkpoints. RNA immunoprecipitation, sequencing of bound transcripts and poly(A) length tests link the melanoma-specific functions of CPEB4 to signalling hubs specifically enriched in this disease. Essential in these CPEB4-controlled networks are the melanoma drivers MITF and RAB7A, a feature validated in clinical biopsies. These results provide new mechanistic links between cytoplasmic polyadenylation and lineage specification in melanoma.

中文翻译：

细胞质多腺苷酸化因子 CPEB4 在黑色素瘤驱动因子调节中的谱系特异性作用。

核 3'-末端多聚腺苷酸化对于几乎所有真核 mRNA 的运输、稳定性和翻译都是必不可少的。Poly(A) 尾部延伸也可能发生在细胞质中，但所涉及的转录本尚不完全清楚，尤其是在癌症中。在这里，我们确定了恶性黑色素瘤中细胞质多腺苷酸结合蛋白 4 (CPEB4) 的谱系特异性要求。正如计算和组织学分析所定义的，CPEB4 在黑色素瘤进展的早期上调。黑色素瘤细胞与其他肿瘤细胞类型的不同之处在于它们对 CPEB4 的依赖性，不仅可以防止有丝分裂畸变，而且可以通过 G1/S 细胞周期检查点。RNA免疫沉淀，结合转录本的测序和 poly(A) 长度测试将 CPEB4 的黑色素瘤特异性功能与特别富含这种疾病的信号枢纽联系起来。这些 CPEB4 控制的网络中必不可少的是黑色素瘤驱动 MITF 和 RAB7A，这是在临床活检中验证的特征。这些结果提供了细胞质多腺苷酸化和黑色素瘤谱系规范之间的新机制联系。

更新日期：2016-11-20

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南