Abstract
Studies have indicated that ectopic expression of p202, an interferon (IFN)-inducible retinoblastoma (Rb)-binding protein, in cultured cells retards cell proliferation and modulates cell survival. Consistent with a role of p202 in cell cycle regulation, levels of p202 increase in cells arrested in the G0/G1 phase of cell cycle after withdrawal of serum growth factors. However, a role for p202 in cell growth arrest remains to be defined. Moreover, it remains unclear how levels of p202 are upregulated during the cell growth arrest. Here, we report that Rb upregulates expression of Ifi202 gene. We found that basal as well as IFN-induced levels of p202 were significantly higher in wild-type (Rb+/+) mouse embryonic fibroblasts (MEFs) than isogenic Rb−/− MEFs. Consistent with the regulation of Ifi202 gene by Rb, expression of functional Rb, but not a pocket mutant of it, stimulated the activity of a reporter whose expression was driven by the 5′-regulatory region of Ifi202 gene. Importantly, the stimulation by Rb was dependent, in part, on a JunD/AP-1 DNA-binding site present in the 5′-regulatory region of the Ifi202 gene. Moreover, basal levels of p202 were significantly higher in wild-type (JunD+/+) than isogenic JunD−/− MEFs. Additionally, we found that increased expression of p202 potentiated the Rb-mediated inhibition of cell growth and mutations in the Rb-binding motif (LxCxE) of p202 significantly reduced cell survival. Together, our observations support the idea that the transcriptional activation of Ifi202 gene by Rb/JunD may be important for the regulation of cell growth and survival.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Almasan A, Yin Y, Kelly RE, Lee EY, Bradley A, Li W, Bertino JR and Wahl GM . (1995). Proc. Natl. Acad. Sci. USA, 92, 5436–5440.
Berry DE, Lu Y, Schmidt B, Fallen PG, O'Connell C, Hu SX, Xu HJ and Blanck G . (1996). Oncogene, 12, 1809–1819.
Castellazzi M, Spyrou G, La Vista N, Dangy JP, Piu F, Yaniv M and Brun G . (1991). Proc. Natl. Acad. Sci. USA, 88, 8890–8894.
Charles A, Tang X, Crouch E, Brody JS and Xiao ZX . (2001). J. Cell. Biochem., 83, 414–425.
Chen PL, Riley DJ, Chen Y and Lee WH . (1996a). Genes Dev., 10, 2794–2804.
Chen PL, Riley DJ, Chen KS and Lee WH . (1996b). Proc. Natl. Acad. Sci. USA, 93, 465–469.
Chen TT and Wang JY . (2000). Mol. Cell. Biol., 20, 5571–5580.
Choubey D . (2000). J. Biol. Regul. Homeost. Agents, 14, 187–192.
Choubey D and Gutterman JU . (1997). Oncogene, 15, 291–302.
Choubey D and Kotzin BL . (2002). Front Biosc., 7, e252–e262.
Choubey D and Lengyel P . (1993). J. Interferon Res., 13, 43–52.
Choubey D and Lengyel P . (1995). J. Biol. Chem., 270, 6134–6140.
Choubey D, Li SJ, Datta B, Gutterman JU and Lengyel P . (1996). EMBO J., 15, 5668–5678.
Choubey D, Snoddy J, Chaturvedi V, Toniato E, Opdenakker G, Thakur A, Samantha H, Engel D and Lengyel P . (1989). J. Biol. Chem., 264, 17182–17189.
Datta B, Li B, Choubey D, Nallur G and Lengyel P . (1996). J. Biol. Chem., 271, 27544–27557.
Datta B, Min W, Burma S and Lengyel P . (1998). Mol. Cell. Biol., 18, 1074–1083.
Decary S, Decesse JT, Ogryzko V, Reed JC, Naguibneva I, Harel-Bellan A and Cremisi CE . (2002). Mol. Cell. Biol., 22, 7877–7888.
Decesse JT, Medjkane S, Datto MB and Cremisi CE . (2001). Oncogene, 20, 962–971.
DiCiommo D, Gallie BL and Bremner R . (2000). Cancer Biol., 10, 255–269.
D'Souza S, Xin H, Walter S and Choubey D . (2001). J. Biol. Chem., 276, 298–305.
Geng Y, D'Souza S, Xin H, Walter S and Choubey D . (2000). Cell Growth Diff., 11, 475–483.
Grander D, Sangfelt O and Erickson S . (1997). Eur. J. Haematol., 59, 129–135.
Gribaudo G, Toniato E, Engel DA and Lengyel P . (1987). J. Biol. Chem., 262, 11878–11883.
Gutterman JU and Choubey D . (1999). Cell Growth Diff., 10, 93–100.
Hamel PA, Gill RM, Phillips RA and Gallie BL . (1992). Oncogene, 7, 693–701.
Haput Y, Rowan S and Oren M . (1995). Oncogene, 10, 1563–1571.
Harbour JW and Dean DC . (2000). Genes Dev., 14, 2393–2409.
Hertel L, Rolle S, De Andrea M, Azzimonti B, Osello R, Gribaudo G, Gariglio M and Landolfo S . (2000). Oncogene, 19, 3598–3608.
Huang HJ, Yee JK, Shew JY, Chen PL, Bookstein R, Friedmann T, Lee EY and Lee WH . (1988). Science, 242, 1563–1566.
Johnstone RW and Trapani JA . (1999). Mol. Cell. Biol., 19, 5833–5838.
Karin M . (1995). J. Biol. Chem., 271, 16483–16486.
Karin M, Liu ZG and Zandi E . (1997). Curr. Opin. Cell Biol., 9, 240–246.
Kim SJ, Lee HD, Robbins PD, Busam K, Sporn MB and Roberts AB . (1991). Proc. Natl. Acad. Sci. USA, 88, 3052–3056.
Kratzke RA, Otterson GA, Hogg A, Coxon AB, Geradts J, Cowell JK and Kaye FJ . (1994). Oncogene, 9, 1321–1326.
Lembo D, Angeretti A, Benefazio S, Hertel L, Gariglio M, Novelli F and Landolfo S . (1995). J. Biol. Regul. Homeost. Agents, 9, 42–46.
Li H and Wicks WD . (2001). Arch. Biochem. Biophys., 394, 1–12.
Lipinski MM and Jacks T . (1999). Oncogene, 18, 7873–7882.
Min W, Ghosh S and Lengyel P . (1996). Mol. Cell. Biol., 16, 359–368.
Nead MA, Baglia LA, Antinore MJ, Ludlow JW and McCance DJ . (1998). EMBO J., 17, 2342–2352.
Nevins JR . (1998). Cell Growth Differ., 9, 585–593.
Nicolaides NC, Correa I, Casadevall C, Travali S, Soprano KJ and Calabretta B . (1992). J. Biol. Chem., 267, 19665–19672.
Nishitani J, Nishinaka T, Cheng CH, Rong W, Yokoyama KK and Chiu R . (1999). J. Biol. Chem., 274, 5454–5461.
Otterson GA, Chen WD, Coxon AB, Khleif SN and Kaye FJ . (1997). Proc. Natl. Acad. Sci. USA, 94, 12036–12040.
Pennaneach V, Salles-Passador I, Munshi A, Brickner H, Regazzoni K, Dick F, Dyson N, Chen TT, Wang JY, Fotedar R and Fotedar A . (2001). Mol. Cell, 7, 715–727.
Pfarr CM, Mechta F, Spyrou G, Lallemand D, Carillo S and Yaniv M . (1994). Cell, 76, 747–760.
Rustgi AK, Dyson N and Bernards R . (1991). Nature, 352, 541–544.
Samanta H, Engel DA, Chao HM, Thakur A, Garcia-Blanco MA and Lengyel P . (1986). J. Biol. Chem., 261, 11849–11858.
Sen GC . (2000). Semin. Cancer Biol., 10, 93–101.
Tan X and Wang JY . (1998). Trends Cell Biol., 8, 116–120.
Udvadia AJ, Rogers KT, Higgins PD, Murata Y, Martin KH, Humphrey PA and Horowitz JM . (1993). Proc. Natl. Acad. Sci. USA, 90, 3265–3269.
Wallace M, Coates PJ, Wright EG and Ball KL . (2001). Oncogene, 20, 3597–3608.
Wang JY . (1997). Curr. Opin. Genet. Dev., 7, 39–45.
Wang J, Guo K, Wills KN and Walsh K . (1997). Cancer Res., 57, 351–354.
Weinberg RA . (1995). Cell, 81, 323–330.
Weitzman JB, Fiette L, Matsuo K and Yaniv M . (2000). Mol. Cell, 6, 1109–1119.
Xin H, D'Souza S, Lei F, Lengyel P and Choubey D . (2001). Oncogene, 20, 6828–6839.
Xin H, Geng Y, Pramanik R and Choubey D . (2003). J. Cell. Biochem., 88, 191–204.
Yee AS, Shin HH and Tevosian SG . (1998). Front. Biosci., 3, D532–D547.
Zheng L and Lee WH . (2001). Exp. Cell Res., 264, 2–18.
Acknowledgements
We thank Drs Qin, Geng, and D'Souza for their help during the initial experiments. We also thank Dr Peter Lengyel for discussions and suggestions. This work was supported, in part, by a grant from the National Institutes of Health (CA69031).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Xin, H., Pramanik, R. & Choubey, D. Retinoblastoma (Rb) protein upregulates expression of the Ifi202 gene encoding an interferon-inducible negative regulator of cell growth. Oncogene 22, 4775–4785 (2003). https://doi.org/10.1038/sj.onc.1206780
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1206780
Keywords
This article is cited by
-
BXSB-type genome causes murine autoimmune glomerulonephritis: pathological correlation between telomeric region of chromosome 1 and Yaa
Genes & Immunity (2014)
-
Loss of the retinoblastoma tumor suppressor: differential action on transcriptional programs related to cell cycle control and immune function
Oncogene (2007)
-
A structure-based method for identifying DNA-binding proteins and their sites of DNA-interaction
Journal of Structural and Functional Genomics (2005)
-
A structure-based method for identifying DNA-binding proteins and their sites of DNA-interaction
Journal of Structural and Functional Genomics (2004)