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Y-box factor YB1 controls p53 apoptotic function


Nuclear localization and high levels of the Y-box-binding protein YB1 appear to be important indicators of drug resistance and tumor prognosis. YB1 also interacts with the p53 tumor suppressor protein. In this paper, we have continued to explore YB1/p53 interactions. We report that transcriptionally active p53 is required for nuclear localization of YB1. We go on to show that nuclear YB1 regulates p53 function. Our data demonstrate that YB1 inhibits the ability of p53 to cause cell death and to transactivate cell death genes, but does not interfere with the ability of p53 to transactivate the CDKN1A gene, encoding the kinase p21WAF1/CIP1 required for cell cycle arrest, nor the MDM2 gene. We also show that nuclear YB1 is associated with a failure to increase the level of the Bax protein in normal mammary epithelial cells after stress activation of p53. Together these data suggest that (nuclear) YB1 selectively alters p53 activity, which may in part provide an explanation for the correlation of nuclear YB1 with drug resistance and poor tumor prognosis.

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  • Asakuno K, Kohno K, Uchiumi T, Kubo T, Sato S, Isono M and Kuwano M . (1994). Biochem. Biophys. Res. Commun., 199, 1428–1435.

  • Bargou RC, Jurchott K, Wagener C, Bergmann S, Metzner S, Bommert K, Mapara MY, Winzer KJ, Dietel M, Dorken B and Royer HD . (1997). Nat. Med., 3, 447–450.

  • Berquin IM, Pang B, Dziubinski ML, Scott LM, Chen YQ, Nolan GP and Ethier SP . (2005). Oncogene, 24, 3177–3186.

  • Chen CY, Gherzi R, Andersen JS, Gaietta G, Jurchott K, Royer HD, Mann M and Karin M . (2000). Genes Dev., 14, 1236–1248.

  • Evdokimova V, Ruzanov P, Imataka H, Raught B, Svitkin Y, Ovchinnikov LP and Sonenberg N . (2001). EMBO J., 20, 5491–5502.

  • Haupt Y, Maya R, Kazaz A and Oren M . (1997). Nature, 387, 296–299.

  • Holm PS, Bergmann S, Jurchott K, Lage H, Brand K, Ladhoff A, Mantwill K, Curiel DT, Dobbelstein M, Dietel M, Gansbacher B and Royer HD . (2002). J. Biol. Chem., 277, 10427–10434.

  • Huschtscha LI, Noble JR, Neumann AA, Moy EL, Barry P, Melki JR, Clark SJ and Reddel RR . (1998). Cancer Res., 58, 3508–3512.

  • Jurchott K, Bergmann S, Stein U, Walther W, Janz M, Manni I, Piaggio G, Fietze E, Dietel M and Royer HD . (2003). J. Biol. Chem., 278, 27988–27996.

  • Kaeser MD and Iggo RD . (2002). Proc. Natl. Acad. Sci. USA, 99, 95–100.

  • Kamura T, Yahata H, Amada S, Ogawa S, Sonoda T, Kobayashi H, Mitsumoto M, Kohno K, Kuwano M and Nakano H . (1999). Cancer, 85, 2450–2454.

  • Kohno K, Izumi H, Uchiumi T, Ashizuka M and Kuwano M . (2003). Bioessays, 25, 691–698.

  • Koike K, Uchiumi T, Ohga T, Toh S, Wada M, Kohno K and Kuwano M . (1997). FEBS Lett., 417, 390–394.

  • Lasham A, Lindridge E, Rudert F, Onrust R and Watson J . (2000). Gene, 252, 1–13.

  • Lasham A, Moloney S, Hale T, Homer C, Zhang YF, Murison JG, Braithwaite AW and Watson J . (2003). J. Biol. Chem., 278, 35516–35523.

  • Levenson V, Davidovich I and Roninson I . (2000). Cancer Res., 60, 5027–5030.

  • Lin J, Chen J, Elenbaas B and Levine AJ . (1994). Genes Dev., 8, 1235–1246.

  • Littlewood TD, Hancock DC, Danielian PS, Parker MG and Evan GI . (1995). Nucleic Acids Res., 23, 1686–1690.

  • Lomonosova E, Subramanian T and Chinnadurai G . (2002). J. Virol., 76, 11283–11290.

  • Mantovani R . (1998). Nucleic Acids Res., 26, 1135–1143.

  • Matsumoto K and Wolffe AP . (1998). Trends Cell. Biol., 8, 318–323.

  • Mertens PR, Alfonso-Jaume MA, Steinmann K and Lovett DH . (1999). J. Am. Soc. Nephrol., 10, 2480–2487.

  • Mertens PR, Harendza S, Pollock AS and Lovett DH . (1997). J. Biol. Chem., 272, 22905–22912.

  • Morgenstern JP and Land H . (1990). Nucleic Acids Res., 18, 3587–3596.

  • O'Carroll SJ, Hall AR, Myers CJ, Braithwaite AW and Dix BR . (2000). Biotechniques, 28, 408–410.

  • Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T, Nishimori H, Tamai K, Tokino T, Nakamura Y and Taya Y . (2000). Cell, 102, 849–862.

  • Oda Y, Ohishi Y, Saito T, Hinoshita E, Uchiumi T, Kinukawa N, Iwamoto Y, Kohno K, Kuwano M and Tsuneyoshi M . (2003). J. Pathol., 199, 251–258.

  • Oda Y, Sakamoto A, Shinohara N, Ohga T, Uchiumi T, Kohno K, Tsuneyoshi M, Kuwano M and Iwamoto Y . (1998). Clin. Cancer Res., 4, 2273–2277.

  • Ohga T, Koike K, Ono M, Makino Y, Itagaki Y, Tanimoto M, Kuwano M and Kohno K . (1996). Cancer Res., 56, 4224–4228.

  • Ohga T, Uchiumi T, Makino Y, Koike K, Wada M, Kuwano M and Kohno K . (1998). J. Biol. Chem., 273, 5997–6000.

  • Okamoto T, Izumi H, Imamura T, Takano H, Ise T, Uchiumi T, Kuwano M and Kohno K . (2000). Oncogene, 19, 6194–6202.

  • Prives C and Hall PA . (1999). J. Pathol., 187, 112–126.

  • Raffetseder U, Frye B, Rauen T, Jurchott K, Royer HD, Jansen PL and Mertens PR . (2003). J. Biol. Chem., 278, 18241–18248.

  • Rogan EM, Bryan TM, Hukku B, Maclean K, Chang AC, Moy EL, Englezou A, Warneford SG, Dalla-Pozza L and Reddel RR . (1995). Mol. Cell. Biol., 15, 4745–4753.

  • Sakura H, Maekawa T, Imamoto F, Yasuda K and Ishii S . (1988). Gene, 73, 499–507.

  • Shibahara K, Sugio K, Osaki T, Uchiumi T, Maehara Y, Kohno K, Yasumoto K, Sugimachi K and Kuwano M . (2001). Clin. Cancer Res., 7, 3151–3155.

  • Shibao K, Takano H, Nakayama Y, Okazaki K, Nagata N, Izumi H, Uchiumi T, Kuwano M, Kohno K and Itoh H . (1999). Int. J. Cancer, 83, 732–737.

  • Sommerville J . (1999). Bioessays, 21, 319–325.

  • Stenina OI, Shaneyfelt KM and DiCorleto PE . (2001). Proc. Natl. Acad. Sci. USA, 98, 7277–7282.

  • Stickeler E, Fraser SD, Honig A, Chen AL, Berget SM and Cooper TA . (2001). EMBO J., 20, 3821–3830.

  • Sutherland BW, Kucab J, Wu J, Lee C, Cheang MC, Yorida E, Turbin D, Dedhar S, Nelson C, Pollak M, Leighton Grimes H, Miller K, Badve S, Huntsman D, Blake-Gilks C, Chen M, Pallen CJ and Dunn SE . (2005) advance online publication, 4 April 2005 (doi:10.1038/sj.onc.1208590).

  • Tao W and Levine AJ . (1999). Proc. Natl. Acad. Sci. USA, 96, 3077–3080.

  • Uchiumi T, Kohno K, Tanimura H, Matsuo K, Sato S, Uchida Y and Kuwano M . (1993). Cell Growth Differ., 4, 147–157.

  • Wolffe AP . (1994). Bioessays, 16, 245–251.

  • Zhang YF, Homer C, Edwards SJ, Hananeia L, Lasham A, Royds J, Sheard P and Braithwaite AW . (2003). Oncogene, 22, 2782–2794.

  • Zhou BP, Liao Y, Xia W, Spohn B, Lee MH and Hung MC . (2001a). Nat. Cell. Biol., 3, 245–252.

  • Zhou BP, Liao Y, Xia W, Zou Y, Spohn B and Hung MC . (2001b). Nat. Cell. Biol., 3, 973–982.

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This work was funded by the Cancer Society of New Zealand (Grant 99/11), the Health Research Council of New Zealand (Grant 04/234), and the New Zealand Lottery Board (Grant AP76795). We also thank Moshe Oren (Israel) and Karen Vousden (Scotland) for promoter-reporter constructs and Lily Huschtscha (Australia) for Bre-80 cells.

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Correspondence to Antony W Braithwaite.

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Homer, C., Knight, D., Hananeia, L. et al. Y-box factor YB1 controls p53 apoptotic function. Oncogene 24, 8314–8325 (2005).

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  • YB1
  • nuclear localization
  • p53 functions
  • apoptosis

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