Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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


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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8


  • Banerjee D, Lenz HJ, Schnieders B, Manno DJ, Ju JF, Spears CP, Hochhauser D, Danenberg K, Danenberg P and Bertino JR . (1995). Cell Growth Differ., 6, 1405–1413.

  • Bocchia M, Xu Q, Wesley U, Xu Y, Korontsvit T, Loganzo F, Albino AP and Scheinberg DA . (1997). Leuk. Res., 21, 439–447.

  • Butler LM, Zhou X, Xu WS, Scher HI, Rifkind RA, Marks PA and Richon VM . (2002). Proc. Natl. Acad. Sci. USA, 99, 11700–11705.

  • Chen KS and DeLuca HF . (1994). Biochim. Biophys. Acta, 1219, 26–32.

  • Corn PG and El-Deiry WS . (2002). BioEssays, 24, 83–90.

  • Costoya JA and Pandolfi PP . (2001). Curr. Opin. Hematol., 8, 212–217.

  • David G, Alland L, Hong SH, Wong CW, DePinho RA and Dejean A . (1998). Oncogene, 16, 2549–2556.

  • Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A and Licht JD . (1999). Blood, 94, 3737–3747.

  • Junn E, Han SH, Im JY, Yang Y, Cho EW, Urn HD, Kim DK, Lee KW, Han PL, Rhee SG and Choi I . (2000). J. Immunol., 164, 6287–6295.

  • Kirshenbaum LA . (2001). Circ. Res., 88, 978–980.

  • Kramer OH, Gottlicher M and Heinzel T . (2001). Trends Endocrinol. Metab., 12, 294–300.

  • Li JY, English MA, Ball HJ, Yeyati PL, Waxman S and Licht JD . (1997). J. Biol. Chem., 272, 22447–22455.

  • Lin RJ, Nagy L, Inoue S, Shao W, Miller Jr WH and Evans RM . (1998). Nature, 391, 811–814.

  • Ludwig DL, Kotanides H, Le T, Chavkin D, Bohlen P and Witte L . (2001). Gene, 269, 103–112.

  • Melnick A, Carlile G, Ahmad KF, Kiang CL, Corcoran C, Bardwell V, Prive GG and Licht JD . (2002). Mol. Cell. Biol., 22, 1804–1818.

  • Melnick A, Carlile GW, McConnell MJ, Polinger A, Hiebert SW and Licht JD . (2000). Blood, 96, 3939–3947.

  • Muller C, Yang R, Park DJ, Serve H, Berdel WE and Koeffler HP . (2000). Blood, 96, 3894–3899.

  • Nishiyama A, Matsui M, Iwata S, Hirota K, Masutani H, Nakamura H, Takagi Y, Sono H, Gon Y and Yodoi J . (1999). J. Biol. Chem., 274, 21645–21650.

  • Olsson I, Bergh G, Ehinger M and Gullberg U . (1996). Eur. J. Haematol., 57, 1–16.

  • Pear WS, Nolan GP, Scott ML and Baltimore D . (1993). Proc. Natl. Acad. Sci. USA, 90, 8392–8396.

  • Piazza F, Gurrieri C and Pandolfi PP . (2001). Oncogene, 20, 7216–7222.

  • Piek JM, van Diest PJ, Verheijen RH and Kenemans P . (2001). Histopathology, 38, 481–482.

  • Rego EM, He LZ, Warrell Jr RP, Wang ZG and Pandolfi PP . (2000). Proc. Natl. Acad. Sci. USA, 91, 10173–10178.

  • Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, Spellman P, Iyer V, Jeffrey SS, Van de Rijn M, Waltham M, Pergamenschikov A, Lee JC, Lashkari D, Shalon D, Myers TG, Weinstein JN, Botstein D and Brown PO . (2000). Nat. Genet., 24, 227–235.

  • Sainty D, Liso V, Cantu-Rajnoldi A, Head D, Mozziconacci MJ, Arnoulet C, Benattar L, Fenu S, Mancini M, Duchayne E, Mahon FX, Gutierrez N, Birg F, Biondi A, Grimwade D, Lafage-Pochitaloff M, Hagemeijer A and Flandrin G . (2000). Blood, 96, 1287–1296.

  • Shaknovich R, Yeyati PL, Ivins S, Melnick A, Lempert C, Waxman S, Zelent A and Licht JD . (1998). Mol. Cell. Biol., 18, 5533–5545.

  • Sherr CJ . (2000). Cancer Res., 60, 3689–3695.

  • Takahashi Y, Nagata T, Ishii Y, Ikarashi M, Ishikawa K and Asai S . (2002). Oncol. Rep., 9, 75–79.

  • Taplick J, Kurtev V, Kroboth K, Posch M, Lechner T and Seiser C . (2001). J. Mol. Biol., 308, 27–38.

  • Wang C, Fu M, Mani S, Wadler S, Senderowicz AM and Pestell RG . (2001). Front. Biosci., 6, D610–D629.

  • Wang X and Studzinski GP . (2001). J. Cell Biochem., 80, 471–482.

  • Wang Y, De Keulenaer GW and Lee RT . (2002). J. Biol. Chem., 277, 26496–26500.

  • Ward JO, McConnell MJ, Carlile GW, Pandolfi PP, Licht JD and Freedman LP . (2001). Blood, 98, 3290–3300.

  • Xu X, Qiao W, Linke SP, Cao L, Li WM, Furth PA, Harris CC and Deng CX . (2001). Nat. Genet., 28, 266–271.

  • Yang X, Young LH and Voigt JM . (1998). Breast Cancer Res. Treat., 48, 33–44.

  • Yeyati PL, Shaknovich R, Boterashvili S, Li J, Ball HJ, Waxman S, Nason-Burchenal K, Dmitrovsky E, Zelent A and Licht JD . (1999). Oncogene, 18, 925–934.

  • Zheng L and Lee WH . (2001). Exp. Cell Res., 264, 2–18.

Download references


This work was partially supported by a Grant FG-3-1-04 of 21C Frontier Functional Human Genome Project from Ministry of Science and Technology of Korea and by a KRF-99-042-D00127 of Korea Research Foundation Grant.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Inpyo Choi.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Han, S., Jeon, J., Ju, H. et al. VDUP1 upregulated by TGF-β1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression. Oncogene 22, 4035–4046 (2003).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • VDUP1
  • tumor
  • TGF-β1
  • cell cycle
  • PLZF

This article is cited by


Quick links