Nuclear proteome analysis reveals a role of Vav1 in modulating RNA processing during maturation of tumoral promyelocytes

• Published in: Journal of proteomics Vol. 75; no. 2; pp. 398 - 409
• Main Authors: Bertagnolo, Valeria, Grassilli, Silvia, Petretto, Andrea, Lambertini, Elisabetta, Astati, Laura, Bruschi, Maurizio, Brugnoli, Federica, Nika, Ervin, Candiano, Giovanni, Piva, Roberta, Capitani, Silvano
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 21.12.2011; Elsevier
• Subjects: APL-derived cells; ATRA; Biological and medical sciences; Cell Differentiation - drug effects; Cell Nucleus - metabolism; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Data processing; Diverse techniques; DNA; Fundamental and applied biological sciences. Psychology; Gene expression; Granulocyte Precursor Cells - drug effects; Granulocyte Precursor Cells - metabolism; Humans; Membrane-depleted nuclei; messenger RNA; Molecular and cellular biology; mRNA processing; mRNA stability; Nuclear Proteins - metabolism; Nuclei; phenotype; Protein expression; proteins; proteome; Proteomic analysis; proteomics; Proto-Oncogene Proteins c-vav - physiology; RNA - metabolism; RNA Interference - drug effects; RNA processing; Tretinoin - pharmacology; Tumors; Two-Dimensional Difference Gel Electrophoresis; Vav1; Protein expression; Membrane-depleted nuclei; Proteomic analysis; ATRA; Vav1; APL-derived cells; RNA; Promyelocyte; Proteome; Protein; Analysis; Proteomics; Membrane; Tumor; Cell
• ISSN: 1874-3919; 1876-7737
• DOI: 10.1016/j.jprot.2011.08.005

Vav1 is a key molecule in the ATRA-induced acquisition of a mature phenotype by tumoral myeloid precursors. Since ATRA acts throughout events that require extensive changes of nuclear architecture and activity and considering that Vav1 accumulates inside the nuclear compartment of differentiating APL-derived cells, the possible role of this protein in modulating the nuclear proteome was investigated. Membrane-depleted nuclei purified from NB4 cells induced to differentiate with ATRA in the presence of forcedly down-modulated Vav1 were subjected to 2D-DIGE followed by mass spectra analysis. The obtained data demonstrated that, in NB4 cells treated with ATRA, Vav1 is involved in determining the nuclear amount of proteins involved in molecular complexes with DNA and may participate to RNA processing by carrying in the nucleus molecules involved in modulating mRNA production and stability, like hnRNPs and SR proteins. Our results provide the first evidence that, at least in maturation of tumoral myeloid precursors, Vav1 is part of interconnected networks of functionally related proteins ended to regulate different aspects of gene expression. Since defects in mRNA processing are common in tumor development, our data suggest that Vav1 is a potential target molecule for developing new anti-cancer strategies. [Display omitted] ► Vav1 sustains the ATRA-induced maturation of APL-derived cells. ► Vav1 is involved in determining the nuclear amount of DNA-interacting proteins. ► Vav1 drives inside the nucleus molecules involved in mRNA production and stability. ► Since mRNA fate is altered in tumors, Vav1 may be a target for anti-cancer strategies.