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

Abstract

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.