Transcription of the human vimentin gene is repressed by ZBP-89 orp53 but activated by the oncogenec-Jun

Vimentin, a member of the intermediate filament protein family exhibits both developmental and tissue-specific expression. Here, we show that for the vimentin promoter, both ZBP-89 and ZBP-99 repress reporter gene expression in Schneider (S2) cells. Deletion constructs confirm that the glutamine-rich region of Sp1 is required to enhance vimentin transcription, whereas the N-terminus of ZBP-89 is required to interact with Sp1 and repress gene expression. The overexpression of hTAFII130 can alleviate ZBP-89 repression in S2 cells, suggesting that ZBP-89 might serve to repress vimentin gene expression by blocking the interaction of hTAFII130 and Sp1.; Previously, tandem AP1 sites in the promoter were reported to be important for the serum and TPA inducibility of the vimentin gene. Here, we find that Sp1 is indispensable for c-Jun to activate vimentin gene expression.; The tumor suppressor p53 has been found to be involved in cell cycle control, apoptosis and tumor progression. Transient in vivo functional assays show that p53 represses vimentin transcription independent of the two putative p53 binding sites in the vimentin promoter.; Stable transformation of the MCF7 cell line with the oncogene c-Jun resulted in a cell line (MCF7Jun), which displayed a change in morphology, enhanced migratory and invasive properties, and metastatic behavior. Here we found that p53 protein together with vimentin was greatly induced in MCF7Jun cells. However, transcription of ZBP-89, p21 and mdm2 were shown to be highly decreased in the MCF7Jun cells by real time-PCR in contrast to the noted increase for vimentin. A decrease in p21 promoter-luciferase activity (a promoter known to be activated by p53), further suggested a decrease in "functional" p53 activity.; In summary, a detailed analysis of vimentin gene expression has revealed new mechanisms of gene control. Vimentin expression is repressed by both ZBP-89 and p53. These may be mutually exclusive repressive events or share a common mediator(s) of repression. On the other hand, c-Jun activates vimentin expression by both a classical, DNA binding mechanism as well as a non-classical interaction where c-Jun serves as a co-activator to superactivate Sp1-mediated activation. In all cases, these represent new paradigms for ZBP-89, p53 and c-Jun regulation of gene expression in general as well as for the vimentin gene. (Abstract shortened by UMI.)...