profiling-ubiquitin-ubiquitin-like-dependent-post-translational

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

Ubiquitin (ub) and ubiquitin-like (ubl) dependent post-translational modifications of proteins play fundamental biological regulatory roles within the ...

Institut Paoli-Calmettes, CRCM

The microRNA-200 (miR-200) family is frequently down-regulated in tumors, including pancreatic adenocarcinomas (PDACs). In this study we have examined the mechanisms involved in the loss of miR-200s in tumoral pancreatic cells. Whereas miR-200 gene promoters appear methylated in mature miR-200 deficient cell lines, miR-200 precursors are detected in nuclear but not cytoplasmic compartment of these cells, indicating that promoter hypermethylation is not sufficient to explain the deficit of mature miR-200s. The ribonuclease Monocyte Chemotactic Protein-induced Protein-1 (MCPiP1) may counteract Dicer1 in miRNA maturation process. MCPiP1/Dicer1 mRNA and protein ratios appear higher in miR-200 deficient compared to miR-200 proficient cells, suggesting that MCPiP1 may compete with Dicer1 in mature miR-200 deficient cells. Inhibition of MCPiP1 allows the detection of miR-200 precursors in cytoplasm of miR-200 deficient cells, confirming its involvement in the loss of miR-200s. Also, reversion of MCPiP1/Dicer1 ratio by over-expression of Dicer1 in miR-200 deficient cells leads to the recovery of mature miR-200s. Finally, whereas human malignant pancreatic tissues (PDACs) express lower miR-200 levels than non malignant tissues (non-MPDs), MCPiP1/Dicer1 ratio appears higher in PDACs, when compared to non-MPDs, supporting the hypothesis that MCPiP1/Dicer1 ratio is determinant in regulating miR-200 maturation process in a subset of tumoral pancreatic cells.

Yolande Berthois

Aix-Marseille Univ,
Inserm,
CNRS,
Aix-Marseille Univ, INSERM, CNRS

Institut Paoli-Calmettes, CRCM

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

Yolande Berthois

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Institut Paoli-Calmettes, CRCM

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

Aix-Marseille Univ,
Inserm,
CNRS,
Aix-Marseille Univ, INSERM, CNRS