Vitamin D 3 up-regulated protein 1 (VDUP1) is a stressresponse gene that is up-regulated by 1,25(OH) 2 D 3 in many cells. It has been reported that VDUP1 expression is reduced in many tumor cells and the enforced expression of VDUP1 inhibits cell proliferation by arresting cell cycle progression. Here, we found that VDUP1 À/À fibroblast cells proliferated more rapidly compared with wild-type cells with reduced expression of p27 kip1 , a cyclin-dependent kinase inhibitor. JAB1 is known to interact with p27 kip1 and to decrease the stability of p27 kip1 . VDUP1 interacted with JAB1 and restored JAB1-induced suppression of p27 kip1 stability. In this process, VDUP1 blocked the JAB1-mediated translocation of p27 kip1 from the nucleus to the cytoplasm. In addition, VDUP1 inhibited JAB1-mediated activator protein-1 activation and cell proliferation. Taken together, these results indicate that VDUP1 is a novel factor of p27 kip1 stability via regulating JAB1. (Cancer Res 2005; 65(11): 4485-9)
Vitamin D3 upregulated protein 1 (VDUP1) is a stress-response gene that is upregulated by 1,25(OH)2D3 in tumor cells. The in vivo roles of VDUP1 were investigated by producing mice lacking VDUP1 (VDUP1-/- mice). VDUP1-/- mice showed minimal changes in the development of T and B cells, but there was a profound reduction in the numbers of natural killer (NK) cells. As well, these mice showed decreased NK activity. In the VDUP1-/- mice, the expression of CD122 was reduced, demonstrating that VDUP1 is required for CD122 expression and NK maturation. In addition, severe lymphoid hyperplasia in the small intestine was observed in VDUP1-/- mice. Taken together, these results suggest that VDUP1 is a critical factor for the development and function of NK cells in vivo.
Vitamin D(3) upregulated protein 1 (VDUP1) is a 46-kDa multifunctional protein, initially isolated in HL-60 cells as a protein of which expression is upregulated by vitamin D(3) administration. Subsequently, it was identified independently by investigators from diverse scientific backgrounds as a thioredoxin binding protein that negatively regulates the expression and the activity of thioredoxin, and is thus involved in redox regulation. Further studies have revealed that VDUP1 plays multiple roles in a wide range of cellular processes such as proliferation or apoptosis. Recently, it has been reported that VDUP1 is also involved in the immune system via positive regulation of natural killer development. In addition, VDUP1 has been revealed to be associated with the fatty acid utilization. In the present review, we discuss the novel aspects of VDUP1 function as well as the historical background of VDUP1. Future studies will explore the diagnostic and therapeutic potential of modulating the function of VDUP1 in vivo.
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