NF-κB전사인자가 coactivator을 통하여 VDUP1 발현을 억제하는 기전

Abstract

Vitamin D3 up-regulated protein 1 (VDUP1) is a stress responsive gene that is up-regulated by 1,25 (OH)2D3, an active form of vitamin D3. It has been reported that the expression of VDUP1 is reduced in many tumor cells and that the enforced expression of VDUP1 inhibits the proliferation of tumor cells. We therefore consider VDUP1 as a tumor suppressor. In the present study, we found that VDUP1 is down- regulated by NF-κB transcription factor in human gastric cancer cell line AGS. On the contrary to VDUP1, NF-κB enhances the growth and proliferation of tumors and its expression is up-regulated in various tumors. To determine the regulatory mechanism by which NF-κB suppresses the transcription of VDUP1, the various deletion constructs of VDUP promoter were designed. As a result of promoter analysis, we found that NF-κB did not bind to VDUP1 promoter region, but it could inhibit the recruitment of coactivators (PCAF, p300 and CBP) to NF-Y, which plays a critical role in the increase of VDUP1 transcription. SAHA-mediated the recruitment of coactivators to NF-Y was also inhibited by NF-κB. These results imply that activation of NF-κB suppresses VDUP1 gene induction by SAHA through preventing the recruitment of coactivators to NF-Y in human gastric cancer cells. (Cancer Prev Res 12, 14-20, 2007)

Key Words: VDUP1, NF-κB, p300, pCAF