VDUP1 upregulated by TGF-β1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression

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Abstract
Vitamin D3 upregulated protein 1 (VDUP1) is a 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) upregulated protein, and it is induced by various stresses. In human tumor tissues, VDUP1 expression was downregulated. Upon stimulation by growth-inhibitory signals such as TGF-β1 and 1,25(OH)2D3, its expression was rapidly upregulated as the cell growth was retarded. The transfection of VDUP1 in tumor cells reduced cell growth. The VDUP1 expression was also increased when the cell-cycle progression was arrested. Transfection of VDUP1 induced cell-cycle arrest at the G0/G1 phase, indicating that VDUP1 possesses a tumor-suppressive activity. In addition, it was found that VDUP1 interacted with promyelocytic leukemia zinc-finger, Fanconi anemia zinc-finger, and histone deacetylase 1, which are known to be transcriptional corepressors. VDUP1 itself suppressed IL-3 receptor and cyclin A2 promoter activity. Taken together, these results suggest that VDUP1 is a novel antitumor gene which forms a transcriptional repressor complex.