[Show abstract][Hide abstract] ABSTRACT: A 340 nucleotide section of the c- myc 5' untranslated region (UTR) contains an internal ribosome entry segment. We have described previously a mutation in this region of RNA in cell lines derived from patients with multiple myeloma (MM) which exhibit increased expression of c- myc protein by an aberrant translational mechanism. In this study we show by electrophoretic mobility shift assays (EMSA), north-western blotting and UV cross-linking that radiolabelled c- myc 5' UTR RNA transcripts which harbour the mutation cause enhanced binding of cellular proteins. In addition, we also demonstrate that an MM derived cell line possesses an altered repertoire of RNA binding proteins. Our data suggest that the deregulated expression of c -myc in MM could result both from the effect of the mutation and the additional proteins which are present in these cell types.
Nucleic Acids Research 08/1998; 26(13):3097-103. · 8.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In cell lines derived from patients with multiple myeloma (MM) we have found an elevation in the amount of the c-myc protein which is not accompanied by an increase in the level of mRNA or a change in the half-life of the protein. There is a 3.4 fold enhancement in the degree of association of the c-myc message with polysomes. This is not accompanied by an alteration in polysome size or a change in the transit time of the c-myc mRNA on the polysomes thus suggesting that there is in increase in the degree of mobilisation of the c-myc message. Sequencing of the c-myc 5'UTR has revealed the presence of a mutation in all the MM cell lines studied and we demonstrate that this mutation causes altered binding of cellular proteins to this RNA species.
Current topics in microbiology and immunology 02/1997; 224:269-76. · 4.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We demonstrate a 10- to 25-fold increase in the amount of c-myc protein in several independent cell lines derived from patients with multiple myeloma (MM). This is not accompanied by a corresponding increase in the overall level of the c-myc mRNA. There is, however, a 3.4-fold increase in the amount of c-myc mRNA associated with the polysomes in these cell lines without any detectable change in either the polysome size or the rate of translation elongation, thus suggesting that there is an increase in the extent of mobilisation of c-myc mRNA to the polysomes in MM. Analysis of the 5' untranslated region of c-myc has revealed the presence of a mutation, in all of the MM cell lines examined, in a region which has been implicated previously in the translational control of this mRNA species. These data suggest aberrant translational control of the c-myc gene in cell lines derived from patients with MM, which may contribute towards pathogenesis of the disease.