zeta-Crystallin is a bcl-2 mRNA binding protein involved in bcl-2 overexpression in T-cell acute lymphocytic leukemia.
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.
Lapucci
Andrea
A
Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy.
Lulli
Matteo
M
Amedei
Amedeo
A
Papucci
Laura
L
Witort
Ewa
E
Di Gesualdo
Federico
F
Bertolini
Francesco
F
Brewer
Gary
G
Nicolin
Angelo
A
Bevilacqua
Annamaria
A
Schiavone
Nicola
N
Morello
Dominique
D
Donnini
Martino
M
Capaccioli
Sergio
S
D020413:3' Untranslated Regions / Q000502:physiology*; D015153:Blotting, Western; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D038226:zeta-Crystallins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D010835:Phytohemagglutinins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D038226:zeta-Crystallins