Post-transcriptional mechanisms in BCR/ABL leukemogenesis: role of shuttling RNA-binding proteins.
Shuttling hnRNPs control the fate of eukaryotic mRNAs throughout their journey from the active site of transcription to that of translation; thus, gain or loss of their function in hematopoietic cells might result in altered hematopoiesis and/or be associated with the process of leukemogenesis. In BCR/ABL-expressing cells, there is a marked increase in the protein levels FUS, hnRNP A1 and hnRNP E2, three RNA-binding proteins involved in the regulation of mRNA processing, nucleocytoplasmic export, and translation. Ectopic expression and/or inhibition of the activity of these RNA-binding proteins affects proliferation, survival, and differentiation of normal and BCR/ABL-expressing cells, suggesting that enhanced expression/activity of certain RNA-binding proteins plays an important, but as yet unrecognized, role in BCR/ABL leukemogenesis. The identification of the mRNA subsets associated with RNA-binding proteins upregulated in BCR/ABL-expressing cells should functionally link the process of leukemogenesis with alteration of mRNA metabolism.
Perrotti
Danilo
D
Thomas Jefferson University, Department of Microbiology and Immunology, Kimmel Cancer Institute, Philadelphia, PA 19107, USA.
Calabretta
Bruno
B
D016044:Fusion Proteins, bcr-abl; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000502:physiology*
D016601:RNA-Binding Proteins; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl