TY - JOUR
T1 - Nuclear proteome analysis reveals a role of Vav1 in modulating RNA processing during maturation of tumoral promyelocytes
AU - Bertagnolo, Valeria
AU - Grassilli, Silvia
AU - Petretto, Andrea
AU - Lambertini, Elisabetta
AU - Astati, Laura
AU - Bruschi, Maurizio
AU - Brugnoli, Federica
AU - Nika, Ervin
AU - Candiano, Giovanni
AU - Piva, Roberta
AU - Capitani, Silvano
PY - 2011/12/21
Y1 - 2011/12/21
N2 - 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.
AB - 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.
KW - APL-derived cells
KW - ATRA
KW - Membrane-depleted nuclei
KW - Protein expression
KW - Proteomic analysis
KW - Vav1
UR - http://www.scopus.com/inward/record.url?scp=82355185803&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82355185803&partnerID=8YFLogxK
U2 - 10.1016/j.jprot.2011.08.005
DO - 10.1016/j.jprot.2011.08.005
M3 - Article
C2 - 21856460
AN - SCOPUS:82355185803
VL - 75
SP - 398
EP - 409
JO - Journal of Proteomics
JF - Journal of Proteomics
SN - 1874-3919
IS - 2
ER -