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Staf50 is a novel p53 target gene conferring reduced clonogenic growth of leukemic U-937 cells

Oncogene volume 23, pages 4050–4059 (2004)Cite this article

Abstract

The tumor suppressor gene p53 is a transcription factor that mediates both cell cycle arrest and apoptosis. Interestingly, p53 also induces differentiation of a number of tissues, including leukemic cells. However, although p53-mediated differentiation of leukemic U-937 cells depends on the transcriptional activity of p53, a p53 target gene mediating differentiation has hitherto not been identified. To screen for novel p53 target genes in leukemic cells, a cDNA microarray analysis was performed with U-937-4/ptsp53 cells, expressing a temperature-sensitive p53 mutant. We report that transcription of the Staf50 (stimulated transacting factor of 50 kDa) gene is upregulated in response to wild-type p53 in U-937-4, K562 and MCF-7 cells. Staf50 was directly activated by p53, as determined by the independence of de novo protein synthesis. Moreover, while the proximal promoter of Staf50 was found not to be p53 responsive, a functional enhancer-like p53-response element in intron 1 of the Staf50 gene was identified that was also transactivated by the p53-family member p73. Direct binding of p53 to the response element was shown by electrophoretic mobility shift analysis. Ectopic expression of Staf50 in U-937 cells resulted in reduced clonogenic growth. Moreover, levels of endogenous Staf50 mRNA correlated to all-trans retinoic acid-induced differentiation of promyelocytic NB-4 and HL60 cells, suggesting that Staf50 could be involved in proliferation and/or differentiation of leukemic cells.

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References

  • Almog N and Rotter V . (1997). Biochim. Biophys. Acta, 1333, 1–27.

  • Asada M, Yamada T, Fukumoro K and Mizutani S . (1998). Leukemia, 12, 1944–1950.

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

  • Casini T and Pelicci PG . (1999). Oncogene, 18, 3235–3243.

  • Chylicki K, Ehinger M, Svedberg H, Bergh G, Olsson I and Gullberg U . (2000a). Cell Growth Differ., 11, 315–324.

  • Chylicki K, Ehinger M, Svedberg H and Gullberg U . (2000b). Cell Growth Differ., 11, 561–571.

  • Ehinger M, Bergh G, Johansson E, Gullberg U and Olsson I . (1997). Cell Growth Differ., 8, 1127–1137.

  • Ehinger M, Bergh G, Olofsson T, Baldetorp B, Olsson I and Gullberg U . (1996). Blood, 87, 1064–1074.

  • Ehinger M, Nilsson E, Persson AM, Olsson I and Gullberg U . (1995). Cell Growth Differ., 6, 9–17.

  • El-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW and Vogelstein B . (1992). Nat. Genet., 1, 45–49.

  • El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KK and Vogelstein B . (1993). Cell, 75, 817–825.

  • Ellisen LW, Carlesso N, Cheng T, Scadden DT and Haber DA . (2001). EMBO J., 20, 1897–1909.

  • Fei P, Eric JB and El-Deiry WS . (2002). Cancer Res., 62, 7316–7327.

  • Feinstein E, Gale RP, Reed J and Canaani E . (1992). Oncogene, 7, 1853–1857.

  • Gongora C, Tissot C, Cerdan C and Mechti N . (2000). J. Interferon Cytokine Res., 20, 955–961.

  • Gullberg U, Lantz M, Lindvall L, Olsson I and Himmler A . (1992). Eur. J. Cell Biol., 58, 307–312.

  • Hansen R and Oren M . (1997). Curr. Opin. Genet. Dev., 7, 46–51.

  • Jackson P, Bos E and Braithwaite AW . (1993). Oncogene, 8, 589–597.

  • Joazeiro CAP and Weissman AM . (2000). Cell, 102, 549–552.

  • Kastan MB, Zhan Q, El-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B and Fornace Jr AJ . (1992). Cell, 71, 587–597.

  • Ko LJ and Prives C . (1996). Genes Dev., 10, 1054–1072.

  • Lang D, Miknyoczki SJ, Huang L and Ruggeri BA . (1998). Oncogene, 16, 1593–1602.

  • Levine AJ . (1997). Cell, 88, 323–331.

  • Liu M, Iavarone A and Freedman LP . (1996). J. Biol. Chem., 271, 31723–31728.

  • Liu TX, Zhang JW, Tao J, Zhang RB, Zhang QH, Zhao CJ, Tong JH, Lanotte M, Waxman S, Chen SJ, Mao M, Hu GH, Zhu L and Chen Z . (2000). Blood, 4, 1496–1504.

  • Lohrum MA and Vousden KH . (2000). Trends Cell Biol., 10, 197–202.

  • Lozzio CB and Lozzio BB . (1975). Blood, 45, 321–334.

  • Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B and Reed JC . (1994). Oncogene, 9, 1799–1805.

  • Moll UM, Erster S and Zaika A . (2001). Biochem. Biophys. Acta, 1552, 47–59.

  • Momand J and Zambetti GP . (1997). J. Cell Biochem., 64, 343–352.

  • Munsch D, Watanabe-Fukunaga R, Bourdon JC, Nagata S, May E, Yonish-Rouach E and Reisdorf P . (2000). J. Biol. Chem., 275, 3867–3872.

  • Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T and Tanaka N . (2000). Science, 288, 1053–1058.

  • Olsson I, Gullberg U, Ivhed I and Nilsson K . (1983). Cancer Res., 43, 5862–5867.

  • Patarca R, Freeman G, Schwartz J, Singh RP, Kong QT, Murphy E, Andersson Y, Sheng P, Singh P, Johnson KA, Guarnagia SM, Durfee T, Blattner F and Cantor H . (1988). Proc. Natl. Acad. Sci. USA, 85, 2733–2737.

  • Pestka S . (2003). Cancer Cell, 4, 85–87.

  • Peters UR, Tschan MP, Kreuzer KA, Baskaynak G, Lass U, Tobler A, Fey MF and Schmidt CA . (1999). Cancer Res., 59, 4233–4236.

  • Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG and Ballabio A . (2001). EMBO J., 20, 2140–2151.

  • Rizzo MG, Zepparoni A, Cristofanelli B, Scardigli R, Crescenzi M, Blandino G, Giuliacci S, Ferrari S, Soddu S and Sacchi A . (1998). Br. J. Cancer, 77, 1429–1438.

  • Salomoni P and Pandolfi PP . (2002). Cell, 108, 165–170.

  • Sharma K and Srikant CB . (1998). Int. J. Cancer, 76, 259–266.

  • Shaulsky G, Goldfinger N, Peled A and Rotter V . (1991). Proc. Natl. Acad. Sci. USA, 88, 8982–8986.

  • Soddu S, Blandino G, Scardigli R, Coen S, Marchetti A, Rizzo MG, Bossi G, Cimino L, Crescenzi M and Sacci A . (1996). J. Cell Biol., 134, 193–204.

  • Song X, Sheppard HM, Norman AW and Liu X . (1999). J. Biol. Chem., 274, 1676–1682.

  • Sundström C and Nilsson K . (1976). Int. J. Can., 15, 565–577.

  • Sugimoto K, Toyoshima H, Sakai R, Miyagawa K, Hagiwara K, Ishikawa F, Takaku F, Yazaki Y and Hirai H . (1992). Blood, 79, 2378–2383.

  • Swiatecka J, Dzieciol J, Anchim T, Dabrowska M, Pietruczuk M and Wolczynski S . (2000). Neoplasma, 47, 15–24.

  • Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K, Shibue T, Honda K and Taniguchi T . (2003). Nature, 424, 516–523.

  • Takenaka I, Morin F, Bernd RS and Kley N . (1995). J. Biol. Chem., 270, 5405–5411.

  • Takimoto R and El-Deiry WS . (2000). Oncogene, 19, 1735–1743.

  • Tissot C and Mechti N . (1995). J. Biol. Chem., 270, 14891–14898.

  • Tissot C, Taviaux SA, Diriong S and Mechti N . (1996). Genomics, 34, 151–153.

  • Tokino T, Thiagalingam S, El-Deiry WS, Waldman T, Kinzler KW and Vogelstein B . (1994). Hum. Mol. Genet., 3, 1537–1542.

  • Tschan MP, Grob TJ, Peters UR, Laurenzi VD, Huegli B, Kreuzer KA, Schmidt CA, Melino G, Fey MF, Tobler A and Cajot JF . (2000). Biochem. Biophys. Res. Commun., 277, 62–65.

  • Wang JA, Fan S, Yuan RQ, Ma YX, Meng Q, Goldberg ID and Rosen EM . (1999). Int. J. Radiat. Biol., 75, 301–316.

  • Wang ZG, Delva L, Gaboli M, Rivi R, Giorgio M, Cordon-Cardo C, Grosveld F and Pandolfi PP . (1998). Science, 279, 1547–1551.

  • Wolf D and Rotter V . (1985). Proc. Natl. Acad. Sci. USA, 82, 790–794.

  • Wu GS, Burns TF, McDonald III ER, Meng RD, Kao G, Muschel R, Yen T and El-Deiry WS . (1999). Oncogene, 18, 6411–6418.

  • Yang A, Kaghad M, Caput D and McKeon F . (2002). Trends Genet., 18, 90–95.

  • Yang A and McKeon F . (2000). Nat. Rev. Mol. Cell. Biol., 1, 199–207.

  • Zauberman A, Flusberg D, Haupt Y, Barak Y and Oren M . (1995). Nucleic Acids Res., 23, 2584–2592.

  • Zhang P, Wong C, Liu D, Finegold M, Harper JW and Elledge SJ . (1999). Genes Dev., 13, 213–224.

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Acknowledgements

We are indebted to Dr Tor Olofsson for invaluable help with cell sorting. This work was supported by grants from the Swedish Cancer Society, the Swedish Research Council (Project #11546), the Swedish Childhood Cancer Foundation, the Georg Danielsson Foundation, the Gunnar Nilsson Cancer Foundation, the John and Augusta Persson Foundation, the Lundberg Foundation, the Tornspiran Foundation, the Greta and Johan Kock Foundation, funding from Lund University Hospital and from the Knut and Alice Wallenberg Foundation through the SWEGENE program.

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Authors and Affiliations

  1. Department of Hematology, Lund University, BMC,

    Susanna Obad, Hans Brunnström, Kristina Drott & Urban Gullberg

  2. C14, Lund, S-221 84, Sweden

    Susanna Obad, Hans Brunnström, Kristina Drott & Urban Gullberg

  3. Department of Oncology, Lund University, Lund, S-221 84, Sweden

    Johan Vallon-Christersson & Åke Borg

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  1. Susanna Obad
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Correspondence to Urban Gullberg.

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Obad, S., Brunnström, H., Vallon-Christersson, J. et al. Staf50 is a novel p53 target gene conferring reduced clonogenic growth of leukemic U-937 cells. Oncogene 23, 4050–4059 (2004). https://doi.org/10.1038/sj.onc.1207524

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