Post-transcriptional mechanisms in BCR/ABL leukemogenesis: role of shuttling RNA-binding proteins

Oncogene. 2002 Dec 9;21(56):8577-83. doi: 10.1038/sj.onc.1206085.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Fusion Proteins, bcr-abl
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / physiopathology
  • Protein-Tyrosine Kinases / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA-Binding Proteins / physiology*

Substances

  • RNA-Binding Proteins
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl