“Bam,” a novel glucocorticoid-induced BH3-only transcript from the BCL2L11/Bim locus, does not appear to be translated

Abstract

Glucocorticoids (GCs) are steroid hormones that induce cell death and cell cycle arrest in lymphoid tissues. By virtue of this property, GCs are widely exploited in the therapy of acute lymphoblastic leukemia (ALL) in children. We reported a novel BH3-only transcript, “Bam,” from the BCL2L11 locus, which was first described in patients with multiple myeloma. The Bam gene consists of two exons, and became of particular interest to us when we found that it was regulated in the majority of children with ALL and many in vitro systems in which GCs induce cell death. Being a BH3-only transcript, Bam retains a BH3 domain identical to that of Bim, although Bam has a unique C-terminus that is totally different from that of its relative Bim. The present work analyzes whether Bam is translated or not. Since we could not detect Bam in the endogenous situation, we evaluated its 5’ untranslated region (UTR). This revealed that there are three out-of-frame initiation codons preceding the Bam open reading frame (ORF). Experiments with constructs without out-of-frame initiation codons and constructs harboring such codons in their 5’ UTR revealed that Bam translation is handicapped by their presence. Moreover, there was no Kozak translational initiation sequence surrounding any of the AUGs. Taken together, results of the present study strongly suggest that this transcript is translated at a very low rate, if at all.

Keywords::

• Glucocorticoid-regulated gene
• translation
• BCL2 family
• Bam
• BCL2L11/Bim

Acknowledgements

We thank B. Gschirr, C. Mantinger and S. Lobenwein for technical assistance, and A. Villunger and S. Geley for valuable and thoughtful discussions.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work was supported by the Austrian Science Fund (P18747) and Higher Education Commission of Pakistan (HEC). The Tyrolean Cancer Research Institute is supported by the Tiroler Landeskrankenanstalten Ges.m.b.H. (TILAK), the Tyrolean Cancer Aid Society, various businesses, financial institutions and the people of Tyrol.