Heat Shock Factor Regulates VDUP1 Gene Expression

The vitamin D3 up-regulated protein 1 (VDUP1) is identified as interacting protein with thioredoxin (TRX) and functions as a natural antagonist of TRX. Its expression is regulated by various stresses including ROS, UV, and heat shock. In the present study, we observed an inducible expression of VDUP1 in Bosc cells by high density and serum deprivation cultures. To determine transcription factors associated with the induction of VDUP1 by stresses, the promoter region of VDUP1 was cloned. Through reporter assays with plasmids having various deletion of its promoter region and analysis of putative cis-elements, heat shock factor element (HSE) was identified. The deletion of HSE abolished transcriptional activity of VDUP1 promoter by stresses and the binding of heat shock factor (HSF) to HSE was confirmed by gel-shift and supershift assays using nuclear extracts prepared from stressed Bosc cells. Also, the enforced expression of HSF or heat shock increased the transcription of endogenous VDUP1. These imply that HSF is an important transcription factor involved in up-regulation of VDUP1 expression by stresses such as high density and serum deprivation cultures.