Author/Authors :
Trotta، نويسنده , , Rossana and Vignudelli، نويسنده , , Tatiana and Candini، نويسنده , , Olivia and Intine، نويسنده , , Robert V. and Pecorari، نويسنده , , Luisa and Guerzoni، نويسنده , , Clara and Santilli، نويسنده , , Giorgia and Byrom، نويسنده , , Mike W. and Goldoni، نويسنده , , Silvia and Ford، نويسنده , , Lance P. and Caligiuri، نويسنده , , Michael A. and Maraia، نويسنده , , Richard J. and Perrotti، نويسنده , , Danilo and Calabretta، نويسنده , , Bruno، نويسنده ,
Abstract :
In a BCR/ABL-expressing myeloid precursor cell line, p53 levels were markedly downmodulated. Expression of MDM2, the negative regulator of p53, was upregulated in a tyrosine kinase-dependent manner in growth factor-independent BCR/ABL-expressing cells, and in accelerated phase and blast crisis CML samples. Increased MDM2 expression was associated with enhanced mdm2 mRNA translation, which required the interaction of the La antigen with mdm2 5′ UTR. Expression of MDM2 correlated with that of La and was suppressed by La siRNAs and by a dominant negative La mutant, which also enhanced the susceptibility to drug-induced apoptosis of BCR/ABL-transformed cells. By contrast, La overexpression led to increased MDM2 levels and enhanced resistance to apoptosis. Thus, La-dependent activation of mdm2 translation might represent an important molecular mechanism involved in BCR/ABL leukemogenesis.
