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Role of ζ‐Crystallin and Other AUBPs in Bcl‐2 Over‐Expression Occurring in B‐cell CLLs
Author(s) -
Gesualdo Federico,
Donnini Martino,
Witort Ewa,
Papucci Laura,
Specogna Rebecca,
Cianchi Fabio,
Lulli Matteo,
Capaccioli Sergio,
Lapucci Andrea
Publication year - 2009
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/fasebj.23.1_supplement.lb332
Subject(s) - messenger rna , crystallin , biology , gene , gene expression , untranslated region , microbiology and biotechnology , cancer research , genetics
We previously identified in the 3'UTR of bcl‐2 mRNA an adenine + uracil‐rich element (ARE) that regulates bcl‐2 expression at the post‐transcriptional level by interacting with specific AU‐Binding Proteins (AUBPs). In most solid tumours and leukemias, bcl‐2 is overexpressed without any obvious gene rearrangement or mutation, suggesting that it could depend on impaired ARE/AUBP interaction based post‐transcriptional control. Investigating this possibility, we have recently disclosed a new bcl‐2 AUBP, ζ‐crystallin, which increased binding to the ARE of bcl‐2 mRNA resulted in bcl‐2 over‐expression in T‐cells of Acute Lymphocytic Leukemias (ALLs) patients as compared to T‐cells from healthy donors. Here, we also show that ζ‐crystallin and Bcl‐2 protein levels are strictly co‐related in B‐cell Chronic Lymphocytic Leukemias (CLLs) and demonstrate that this is consequent to bcl‐2 mRNA stabilization by ζ‐crystallin, in a circuit involving shifting of other bcl‐2 AUBPs. Our results clearly indicate that ζ‐crystallin overproduction contributes to bcl‐2 over‐expression and thus to the onset of human B‐cell CLLs.