Post-transcriptional and post-translational regulation of Bcl2

Bcl2 is an important pro survival protein that has an essential function in normal immunity and whose constitutive expression leads to the development of lymphomas Although transcriptional control of Bcl2 has been reported increasing evidence suggests an important component of Bcl2 regulation is post transcriptional Phosphorylation of Bcl2 has been shown to enhance activity to allow response to extracellular growth factor mediated signals Bcl2 mRNA contains regulatory elements in both its 5 and 3 UTRs (untranslated regions) An IRES (internal ribosome entry sequence) in the 5 UTR permits continued translation in the presence of cellular stresses that reduce cap dependent translation The 3 UTR of Bcl2 mRNA is 5 2 kb in length and contains multiple predicted miRNA (microRNA) and RNA BP (RNA binding protein) binding sites miR 15a and miR 16 1 have been found to inhibit Bcl2 expression in B cells whereas the RNA BP nucleolin has been shown to increase Bcl2 expression by binding to the 3 UTR and enhancing mRNA stability Both decreased expression of milt 15a and miR 16 1 and increased nucleolin have been shown to be associated with increased Bcl2 expression and resistance to apoptosis in the common human disease chronic lymphocytic leukaemia miRNA based therapeutic approaches to treat cancer are emerging Bcl2 is highly regulated by miRNAs and is therefore an excellent candidate for such approaches