Absence of the first two zinc fingers in BCL6 causes the loss of inhibitory effects on cell growth

Abstract

BCL6ZF is a novel transcript of BCL6, which lacks the first two zinc fingers of BCL6. It has been established that BCL6 acts as a sequence-specific transcriptional repressor, however, the functions of BCL6ZF remain undefined. By generating stably overexpressed BCL6 and BCL6ZF in NCI-H1299 lung cancer cells, it was found that BCL6 suppressed the levels of cell growth associated with impaired G1 phase progression compared with those of the mock control cells. However, the effects of BCL6ZF on cell growth and the cell cycle were negligible. Further study of these results demonstrated that eight genes downstream of BCL6 were markedly downregulated by the overexpression of BCL6, whereas BCL6ZF suppressed only TGFBI, indicating that the loss of the first two zinc fingers caused the loss of the inhibitory effects on cell growth and transcriptional repression. In addition, it was determined that the BCL6ZF protein was not degraded as easily as BCL6 protein by the ubiquitin/proteasome pathway, implying that the loss of the first two zinc fingers changes the three-dimensional structure of BCL6ZF. The results demonstrated that BCL6 and BCL6ZF had different role in H1299 cells both in vitro and in vivo. The loss of its inhibitory effects on cell growth and transcriptional repressions.