zeta-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 zeta-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 zeta-crystallin level. The specific association of zeta-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 zeta-crystallin to bcl-2 overexpression occurring in this leukemia.

• Authors: Andrea Lapucci, Matteo Lulli, Amedeo Amedei, Laura Papucci, Ewa Witort, Federico Di Gesualdo, Francesco Bertolini, Gary Brewer, Angelo Nicolin, Annamaria Bevilacqua, Nicola Schiavone, Dominique Morello, Martino Donnini, Sergio Capaccioli
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 24 Issue 6 Pg. 1852-65 (Jun 2010) ISSN: 1530-6860 [Electronic] United States
• PMID: 20103721 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• Phytohemagglutinins
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• RNA, Small Interfering
• zeta-Crystallins

Topics

• 3' Untranslated Regions (physiology)
• Blotting, Western
• Cytoplasm (drug effects, metabolism)
• Female
• Gene Expression Regulation
• Humans
• Immunoprecipitation
• Male
• Middle Aged
• Phytohemagglutinins
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (genetics, metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• T-Lymphocytes (drug effects, pathology)
• zeta-Crystallins (antagonists & inhibitors, genetics, metabolism)