ζ‐Crystallin is a bcl‐2 mRNA binding protein involved in bcl‐2 overexpression in T‐cell acute lymphocytic leukemia

Abstract

The human antiapoptotic bcl‐2 gene has been discovered in t(14;18) B‐cell leukemias/lymphomas because of its overexpression caused at a transcriptional control level by the bcl‐2/IgH fusion gene. We were the first to disclose the post‐transcriptional control of bcl‐2 expression mediated by interactions of an adenine + uracil (AU)‐rich element (ARE) in the 3′‐UTR of bcl‐2 mRNA with AU‐binding proteins (AUBPs). Here, we identify and characterize ζ‐crystallin as a new bcl‐2 AUBP, whose silencing or overexpression has impact on bcl‐2 mRNA stability. An increased Bcl‐2 level observed in normal phytohemagglutinin (PHA)‐activated T lymphocytes, acute lymphatic leukemia (ALL) T‐cell lines, and T cells of patients with leukemia in comparison with normal non‐PHA‐activated T lymphocytes was concomitant with an increase in ζ‐crystallin level. The specific association of ζ‐crystallin with the bcl‐2 ARE was significantly enhanced in T cells of patients with ALL, which accounts for the higher stability of bcl‐2 mRNA and suggests a possible contribution of ζ‐crystallin to bcl‐2 overexpression occurring in this leukemia.—Lapucci, A., Lulli, M., Amedei, A, Papucci, L., Witort, E., Di Gesualdo, F., Bertolini, F., Brewer, G., Nicolin, A., Bevilacqua, A., Schiavone, N., Morello, D., Donnini, M., Capaccioli, S. ζ‐Crystallin is a bcl‐2 mRNA binding protein involved in bcl‐2 overexpression in T‐cell acute lymphocytic leukemia. FASEB J. 24, 1852–1865 (2010). www.fasebj.org