Chronic myeloid leukemia is a hematopoietic stem cell cancer, originated by the perpetually "switched on" activity of the tyrosine kinase Bcr-Abl, leading to uncontrolled proliferation and insensitivity to apoptotic stimuli. The genetic phenotype of myeloid leukemic K562 cells includes the suppression of cytosolic sialidase Neu2. Neu2 transfection in K562 cells induced a marked decrease (-30% and -80%) of the mRNA of the anti-apoptotic factors Bcl-XL and Bcl-2, respectively, and an almost total disappearance of Bcl-2 protein. In addition, gene expression and activity of Bcr-Abl underwent a 35% diminution, together with a marked decrease of Bcr-Abl-dependent Src and Lyn kinase activity. Thus, the antiapoptotic axis Bcr-Abl, Src, and Lyn, which stimulates the formation of Bcl-XL and Bcl-2, was remarkably weakened. The ultimate consequences of these modifications were an increased susceptibility to apoptosis of K562 cells and a marked reduction of their proliferation rate. The molecular link between Neu2 activity and Bcr-Abl signaling pathway may rely on the desialylation of some cytosolic glycoproteins. In fact, three cytosolic glycoproteins, in the range 45–66 kDa, showed a 50–70% decrease of their sialic acid content upon Neu2 expression, supporting their possible role as modulators of the Bcr-Abl complex.
Expression of sialidase NEU2 in Leukaemic K562 cells induces apoptosis by impairing BCR-ABL/SRC kinases signalling / C. Tringali, B. Lupo, L. Anastasia, N. Papini, E. Monti, R. Bresciani, G. Tettamanti, B. Venerando. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 282:19(2007 May 11), pp. 14364-14372.
|Titolo:||Expression of sialidase NEU2 in Leukaemic K562 cells induces apoptosis by impairing BCR-ABL/SRC kinases signalling|
TRINGALI, CRISTINA ALESSANDRA (Primo)
TETTAMANTI, GUIDO (Penultimo)
VENERANDO, BRUNO (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
|Data di pubblicazione:||11-mag-2007|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1074/jbc.M700406200|
|Appare nelle tipologie:||01 - Articolo su periodico|