Vav1 modulates protein expression during ATRA-lnduced maturation of APL-derived promyelocytes: A proteomic-based analysis

Valeria Bertagnolo, Silvia Grassilli, Alberto Bavelloni, Federica Brugnoli, Manuela Piazzi, Giovanni Candiano, Andrea Petretto, Mascia Benedusi, Silvano Capitani

Research output: Contribution to journalArticle

Abstract

Overexpression of Vav1 promotes the overcoming of the differentiation blockade that characterizes acute promyelocyte 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 promyelocyte 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 14-3-3e, α-enolase, α-tubulin and splice isoform 2 of α3 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.

Original languageEnglish
Pages (from-to)3729-3736
Number of pages8
JournalJournal of Proteome Research
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 2008

Fingerprint

Granulocyte Precursor Cells
Proteomics
Phosphorylation
Proteins
Tyrosine
Cells
Modulation
Cell Line
Cell Cycle Proteins
Phosphopyruvate Hydratase
HL-60 Cells
Myeloid Cells
Proteasome Endopeptidase Complex
Tubulin
Cytoskeleton
Spectrum analysis
Mass Spectrometry
Protein Isoforms
Leukemia
Neutrophils

Keywords

  • APL-derived cell
  • ATRA
  • Protein expression
  • Proteomic analysis
  • Vav1

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Vav1 modulates protein expression during ATRA-lnduced maturation of APL-derived promyelocytes : A proteomic-based analysis. / Bertagnolo, Valeria; Grassilli, Silvia; Bavelloni, Alberto; Brugnoli, Federica; Piazzi, Manuela; Candiano, Giovanni; Petretto, Andrea; Benedusi, Mascia; Capitani, Silvano.

In: Journal of Proteome Research, Vol. 7, No. 9, 09.2008, p. 3729-3736.

Research output: Contribution to journalArticle

Bertagnolo, Valeria ; Grassilli, Silvia ; Bavelloni, Alberto ; Brugnoli, Federica ; Piazzi, Manuela ; Candiano, Giovanni ; Petretto, Andrea ; Benedusi, Mascia ; Capitani, Silvano. / Vav1 modulates protein expression during ATRA-lnduced maturation of APL-derived promyelocytes : A proteomic-based analysis. In: Journal of Proteome Research. 2008 ; Vol. 7, No. 9. pp. 3729-3736.
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