Translational regulation by the p210 BCR/ABL oncoprotein.
The ability of oncogenic proteins to regulate the rate of translation of specific mRNA subsets may be a rapid and efficient mechanism to modulate the levels and, in many cases, the activity of the corresponding proteins. In the past few years, we have identified several RNA binding proteins with translation regulatory activity whose expression is markedly activated in the blast crisis of chronic myelogenous leukemia, which represents the most malignant disease stage. Perturbation of the activity of some RNA binding proteins suppresses the leukemogenic potential of BCR/ABL-expressing cells. Most importantly, we have identified some of the targets of these RNA binding proteins. Two of these targets, c/ebp alpha and mdm2 mRNAs, are directly relevant for the altered differentiation and survival of leukemic cells. The identification of mRNA targets translationally regulated by RNA binding proteins overexpressed in tumor cells may lead to the development of therapeutic strategies aimed at modulating the translation rate of specific mRNAs.
Perrotti
Danilo
D
Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics and the Comprehensive Cancer Center, The Ohio State University, Columbus OH 43210, USA. perrotti-1@medctr.osu.edu
Calabretta
Bruno
B
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000502:physiology; D016044:Fusion Proteins, bcr-abl / Q000502:physiology*; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000502:physiology; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000502:physiology; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins
D020121:5' Untranslated Regions; D022763:CCAAT-Enhancer-Binding Protein-alpha; D004268:DNA-Binding Proteins; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C094604:PCBP1 protein, human; D016601:RNA-Binding Proteins; D016044:Fusion Proteins, bcr-abl