Jab1 is a co-activator of activating protein-1 (AP-1) transcription factor and 
the fifth subunit of the constitutive photomorphogenesis 9 (COP9) signalosome, 
which has been shown to mediate nuclear exportation and ubiquitin-dependent 
degradation of the tumor suppressor p27(Kip1). Jab1 is overexpressed in several 
types of human cancer. However, de-regulation of Jab1 gene expression in cancer 
cells is largely unclear. In this study, we reported that expression of Jab1 was 
stimulated by HER-2/neu oncogene via transcriptional activation. Promoter 
deletion and mutation analysis indicated that HER-2/neu stimulated Jab1 via the 
T cell factor (TCF) binding site located at the -380/-368 region of the human 
Jab1 promoter. DNA affinity precipitation assay and chromatin 
immunoprecipitation assay verified that binding of beta-catenin and TCF-4 to 
this consensus site was increased by HER-2/neu. In addition, dominant-negative 
mutant of TCF significantly attenuated the stimulatory effect of HER-2/neu. We 
also demonstrated that HER-2/neu increased beta-catenin/TCF-mediated Jab1 
expression via the AKT signaling pathway because chemical inhibitor or 
dominant-negative mutant of AKT effectively attenuated the stimulatory action of 
HER-2/neu. IGF-I, which is a well-known AKT activator, also up-regulated the 
expression of Jab1 in NIH/3T3 and MCF-7 cells. Knockdown of Jab1 by small 
interfering RNA (siRNA) preferentially inhibited proliferation of 
HER-2/neu-overexpressing breast cancer cells. Taken together, our results 
suggest that HER-2/neu transcriptionally activates Jab1 expression to promote 
proliferation of breast cancer cells.