Artículos de revistas
Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers
Fecha
2016-11Registro en:
Pérez Guijarro, Eva; Karras, Panagiotis; Cifdaloz, Metehan; Martínez Herranz, Raúl; Cañon, Estela; et al.; Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers; Nature Publishing Group; Nature Communications; 7; 11-2016; 1-17
2041-1723
CONICET Digital
CONICET
Autor
Pérez Guijarro, Eva
Karras, Panagiotis
Cifdaloz, Metehan
Martínez Herranz, Raúl
Cañon, Estela
Graña, Osvaldo
Horcajada Reales, Celia
Alonso Curbelo, Direna
Calvo, Tonantzin G.
Gómez-López, Gonzalo
Bellora, Nicolás
Riveiro-Falkenbach, Erica
Ortiz-Romero, Pablo L.
Rodríguez-Peralto, José L.
Maestre, Lorena
Roncador, Giovanna
De Agustín Asensio, Juan C.
Goding, Colin R.
Eyras, Eduardo
Megiás, Diego
Méndez, Raúl
Soengas, Maria S.
Resumen
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.