Vav1 modulates protein expression during ATRA-induced maturation of APL-derived promyelocytes: a proteomic-based analysis.
Overexpression of Vav1 promotes the overcoming of the differentiation blockade that characterizes acute promyelocytic leukemia cells. At variance, down-modulation of Vav1 prevents ATRA-induced maturation, and in particular, the inhibition of its tyrosine phosphorylation prevents the neutrophil differentiation-related changes of cell morphology. These findings allowed to identify Vav1 as a crucial protein in the ATRA-dependent differentiation of tumoral promyelocytes. By means of a proteomic approach, here we have investigated a possible role for Vav1 in modulating protein expression during ATRA treatment of tumoral promyelocytes. We have performed high-resolution 2-DE coupled with mass spectra analysis of HL-60 and NB4 promyelocytic cell lines induced to differentiate with ATRA when the amounts or the tyrosine phosphorylation of Vav1 were forcedly reduced. We have found that the down-regulation of Vav1 affects the expression level of a number of proteins, including cell cycle/apoptosis- and cytoskeleton-related proteins. In particular, the expression of 14-3-3epsilon, alpha-enolase, alpha-tubulin and splice isoform 2 of alpha3 proteasome subunit changed as a consequence of the down-modulation of Vav1 during the differentiation of both HL-60 and NB4 cell lines, suggesting that these proteins may constitute a common part of the ATRA-induced pathway during maturation of APL-derived promyelocytes. These results indicate an unprecedented role for Vav1 in the maturation of myeloid cells as a regulator of protein expression.
Bertagnolo
Valeria
V
Signal Transduction Unit-Laboratory of Cell Biology, Section of Human Anatomy, Department of Morphology and Embryology, University of Ferrara, Italy, Laboratory of Cell Biology and Electron Microscopy, IOR, Bologna, Italy.
Grassilli
Silvia
S
Bavelloni
Alberto
A
Brugnoli
Federica
F
Piazzi
Manuela
M
Candiano
Giovanni
G
Petretto
Andrea
A
Benedusi
Mascia
M
Capitani
Silvano
S
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007150:Immunohistochemistry; D010766:Phosphorylation; D040901:Proteomics; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D053719:Tandem Mass Spectrometry; D014212:Tretinoin / Q000494:pharmacology*
D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human; D014212:Tretinoin