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ζ‐Crystallin is a bcl‐2 mRNA binding protein involved in bcl‐2 overexpression in T‐cell acute lymphocytic leukemia
Author(s) -
Lapucci Andrea,
Lulli Matteo,
Amedei Amedeo,
Papucci Laura,
Witort Ewa,
Di Gesualdo Federico,
Bertolini Francesco,
Brewer Gary,
Nicolin Angelo,
Bevilacqua Annamaria,
Schiavone Nicola,
Morello Dominique,
Donnini Martino,
Capaccioli Sergio
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-140459
Subject(s) - leukemia , messenger rna , microbiology and biotechnology , biology , gene silencing , t cell , gene , untranslated region , chronic lymphocytic leukemia , cancer research , immunology , biochemistry , immune system
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