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.