Overexpression of RelA Causes G sub(1) Arrest and Apoptosis in a Pro-B Cell Line

• Published in: The Journal of biological chemistry Vol. 274; no. 13; pp. 8708 - 8716
• Main Authors: Sheehy, A M, Schlissel, MS
• Format: Journal Article
• Language: English
• Published: 26.03.1999
• ISSN: 0021-9258

NF- Kappa B/Rel family proteins form a network of post-translationally regulated transcription factors that respond to a variety of extracellular stimuli and mediate distinct cellular responses. These responses include cytokine gene expression, regulated cell cycle activation, and both the protection from and induction of the cell death program. To examine the function of individual Rel family proteins in B cell development and resolve their role in the signaling of apoptosis, we used a tetracycline- regulated gene expression system to overexpress either c-Rel or RelA in the transformed pro-B cell line 220-8. Elevated levels of RelA, but not c-Rel, induced a G sub(1) cell cycle arrest followed by apoptosis. Both the DNA binding and transactivation domains of RelA were required for this effect. When RelA was overexpressed in the immature B cell line WEHI 231 or the mature B cell line M12, neither cell cycle arrest nor apoptosis was evident. The differential effects of elevated RelA levels in these cell lines suggests that susceptibility to NF- Kappa B-induced apoptosis may reflect a relevant selection event during B cell development.