Expression of human BRE in multiple isoforms

BRE, a putative stress-modulating gene, found able to down-regulate TNF-alp ha -induced NF-kappaB activation upon overexpression, is now shown in human cells expressed as multiple m-RNA isoforms. A total of six isoforms are pr oduced by alternative splicing predominantly at either end of the gene. Pre dicted from the cDNA sequences of these isoforms, three of them (alphaa, al phab, and alphac) code for BRE of different C-terminus, and the other three (betaa, betab, and betac) may possibly be the nonfunctional counterparts. All human cells examined coexpress all the predominant splice variants, alb eit at different ratios. Comparing with normal cells, immortalized human ce ll lines uniformly express higher levels of BRE. Interestingly, peripheral blood monocytes responded to LPS by down-regulating the expression of all t he BRE isoforms, which was however less obvious in the cell fine counterpar t, THP-1. Isoform aa, which codes for the canonical BRE with a C-terminal p eroxisomal targeting sequence, is the most abundant transcript. We propose that the function of BRE and its isoforms is to regulate peroxisomal activi ties. (C) 2001 Academic Press.