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Pax‐5B predisposes B lymphocytes to a survival pathway
Author(s) -
Bedard Melanie,
O'Brien Jeannick,
Robichaud Gilles A
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.lb277
Subject(s) - carcinogenesis , biology , transcription factor , microbiology and biotechnology , programmed cell death , apoptosis , gene , function (biology) , cancer research , transcription (linguistics) , genetics , linguistics , philosophy
The Pax‐5 gene codes for a powerful transcription factor that plays a key role in the development and maturation of B cells as well as in oncogenic processes. Under the control of two alternative promoters, Pax‐5 can simultaneously generate two different variant proteins (Pax‐5A and Pax‐5B) which are both important in the modulation of fundamental biological processes such as cellular survival and apoptosis. However, few studies have scrutinized the specific function between Pax‐5 expressed variants in B lymphocytes. We have developed a Pax‐5B suppressed cell model system in B cells based on ribozyme technology. Through the use of this study model, we set out to elucidate the specific roles of the Pax‐5B variant in B lymphocyte activity and oncogenesis. Our results show that Pax‐5B ‐deficient cells are more susceptible to undergo programmed cell death. We observed that Pax‐5B down‐regulated pro‐apoptotic genes (Bax, p53, PD‐1) while suppressing anti‐apoptotic element (Bcl‐2). This study brings insight to a better understand of B cell processes and cancer pathogenesis. These findings also help elucidate signaling cascades involved in Pax‐5 ‐associated oncogenesis and potentially support the discovery of new therapeutic targets.