Abstract
The tumor suppressor p53-related p73 shares significant amino-acid sequence identity with p53. Like p53, p73 recognizes canonical p53 DNA-binding sites and activates p53-responsive target genes and induces apoptosis. Moreover, transcription coactivator p300/CBP binds to and coactivates with both p53 and p73 in stimulating the expression of their target genes. Here, we report that coactivator PCAF binds to p73. The N-terminal transactivation domain (TAD) and the conserved oligomerization domain (OD) of p73 are both required for its interaction with PCAF. Conversely, PCAF's HAT-domain is required for and both the N-terminal region and Bromo domain enhance binding of PCAF to p73. Significantly, PCAF stimulates p73-mediated transactivation, and binding of PCAF to p73 is necessary for p73's transactivation activity. PCAF-specific siRNA dramatically reduces p73-mediated transactivation. Stimulation of p73-mediated transactivation by PCAF requires the HAT domain of PCAF and the p53-binding site within the p21 promoter. In vivo, coexpression of wild-type, but not HAT-deficient PCAF with p73β markedly increases p21 expression. Furthermore, cotransfection of PCAF and p73 leads to increased apoptosis and reduced colony formation. Collectively, these data suggest that p73 recruit PCAF to specific promoters to activate the transcription of p73 target genes.
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References
Agami R, Blandino G, Oren M and Shaul Y . (1999). Nature, 399, 809–813.
Arrowsmith CH . (1999). Cell Death Differ., 6, 1169–1173.
Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS and Kelly K . (1997). Cell, 89, 1175–1184.
Blanco JC, Minucci S, Lu J, Yang XJ, Walker KK, Chen H, Evans RM, Nakatani Y and Ozato K . (1998). Genes Dev., 12, 1638–1651.
Bres V, Tagami H, Peloponese JM, Loret E, Jeang KT, Nakatani Y, Emiliani S, Benkirane M and Kiernan RE . (2002). EMBO J., 21, 6811–6819.
Brown CE, Lechner T, Howe L and Workman JL . (2000). Trends Biochem. Sci., 25, 15–19.
Costanzo A, Merlo P, Pediconi N, Fulco M, Sartorelli V, Cole PA, Fontemaggi G, Fanciulli M, Schiltz L, Blandino G, Balsano C and Levrero M . (2002). Mol. Cell, 9, 175–186.
De Laurenzi V, Costanzo A, Barcaroli D, Terrinoni A, Falco M, Annicchiarico-Petruzzelli M, Levrero M and Melino G . (1998). J. Exp. Med., 188, 1763–1768.
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 KW and Vogelstein B . (1993). Cell, 75, 817–825.
Espinosa JM and Emerson BM . (2001). Mol. Cell, 8, 57–69.
Gong JG, Costanzo A, Yang HQ, Melino G, Kaelin Jr WG, Levrero M and Wang JY . (1999). Nature, 399, 806–809.
Gu J, Rubin RM and Yuan ZM . (2001). Oncogene, 20, 3519–3527.
Gu W and Roeder RG . (1997). Cell, 90, 595–606.
Gu W, Shi XL and Roeder RG . (1997). Nature, 387, 819–823.
Harton JA, Zika E and Ting JP . (2001). J. Biol. Chem., 276, 38715–38720.
Higashino F, Pipas JM and Shenk T . (1998). Proc. Natl. Acad. Sci. USA, 95, 15683–15687.
Huang S, Qiu Y, Shi Y, Xu Z and Brandt SJ . (2000). EMBO J., 19, 6792–6803.
Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W, Flores ER, Tsai KY, Jacks T, Vousden KH and Kaelin Jr WG . (2000). Nature, 407, 645–648.
James P, Halladay J and Craig EA . (1996). Genetics, 144, 1425–1436.
Jeffrey PD, Gorina S and Pavletich NP . (1995). Science, 267, 1498–1502.
Jost CA, Marin MC and Kaelin Jr WG . (1997). Nature, 389, 191–194.
Kaelin Jr WG . (1999). Oncogene, 18, 7701–7705.
Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F and Caput D . (1997). Cell, 90, 809–819.
Ko LJ and Prives C . (1996). Genes Dev., 10, 1054–1072.
Kobet E, Zeng X, Zhu Y, Keller D and Lu H . (2000). Proc. Natl. Acad. Sci. USA, 97, 12547–12552.
Korzus E, Torchia J, Rose DW, Xu L, Kurokawa R, McInerney EM, Mullen TM, Glass CK and Rosenfeld MG . (1998). Science, 279, 703–707.
Levine AJ . (1997). Cell, 88, 323–331.
Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY and Melino G . (2000). J. Cell Sci., 113 (Part 10), 1661–1670.
Liu Y, Colosimo AL, Yang XJ and Liao D . (2000). Mol. Cell. Biol., 20, 5540–5553.
Marin MC, Jost CA, Irwin MS, DeCaprio JA, Caput D and Kaelin Jr WG . (1998). Mol. Cell. Biol., 18, 6316–6324.
Marin MC and Kaelin Jr WG . (2000). Biochim. Biophys. Acta, 1470, M93–M100.
Martinez-Balbas MA, Bauer UM, Nielsen SJ, Brehm A and Kouzarides T . (2000). EMBO J., 19, 662–671.
Minty A, Dumont X, Kaghad M and Caput D . (2000). J. Biol. Chem., 275, 36316–36323.
Munshi N, Agalioti T, Lomvardas S, Merika M, Chen G and Thanos D . (2001). Science, 293, 1133–1136.
Muth V, Nadaud S, Grummt I and Voit R . (2001). EMBO J., 20, 1353–1362.
Ozaki T, Naka M, Takada N, Tada M, Sakiyama S and Nakagawara A . (1999). Cancer Res., 59, 5902–5907.
Polesskaya A, Duquet A, Naguibneva I, Weise C, Vervisch A, Bengal E, Hucho F, Robin P and Harel-Bellan A . (2000). J. Biol. Chem., 275, 34359–34364.
Prabhu NS, Somasundaram K, Satyamoorthy K, Herlyn M and El-Deiry WS . (1998). Int. J. Oncol., 13, 5–9.
Prives C and Hall PA . (1999). J. Pathol., 187, 112–126.
Puri PL, Sartorelli V, Yang XJ, Hamamori Y, Ogryzko VV, Howard BH, Kedes L, Wang JY, Graessmann A, Nakatani Y and Levrero M . (1997). Mol. Cell, 1, 35–45.
Querido E, Morisson MR, Chu-Pham-Dang H, Thirlwell SW, Boivin D and Branton PE . (2001). J. Virol., 75, 699–709.
Sartorelli V, Puri PL, Hamamori Y, Ogryzko V, Chung G, Nakatani Y, Wang JY and Kedes L . (1999). Mol. Cell, 4, 725–734.
Schiltz RL and Nakatani Y . (2000). Biochim. Biophys. Acta, 1470, M37–M53.
Spilianakis C, Papamatheakis J and Kretsovali A . (2000). Mol. Cell. Biol., 20, 8489–8498.
Stambolic V, MacPherson D, Sas D, Lin Y, Snow B, Jang Y, Benchimol S and Mak TW . (2001). Mol. Cell, 8, 317–325.
Sterner DE and Berger SL . (2000). Microbiol. Mol. Biol. Rev., 64, 435–459.
Struhl K . (1998). Genes Dev., 12, 599–606.
Takada N, Ozaki T, Ichimiya S, Todo S and Nakagawara A . (1999). Cancer Res., 59, 2810–2814.
Ueda Y, Hijikata M, Takagi S, Chiba T and Shimotohno K . (1999). Oncogene, 18, 4993–4998.
Ueda Y, Hijikata M, Takagi S, Chiba T and Shimotohno K . (2001). Biochem. J., 356, 859–866.
Vogelstein B, Lane D and Levine AJ . (2000). Nature, 408, 307–310.
Vousden KH . (2000). Cell, 103, 691–694.
Wienzek S, Roth J and Dobbelstein M . (2000). J. Virol., 74, 193–202.
Yang A and McKeon F . (2000). Nat. Rev. Mol. Cell. Biol., 1, 199–207.
Yu J, Zhang L, Hwang PM, Rago C, Kinzler KW and Vogelstein B . (1999). Proc. Natl. Acad. Sci. USA, 96, 14517–14522.
Yuan ZM, Shioya H, Ishiko T, Sun X, Gu J, Huang YY, Lu H, Kharbanda S, Weichselbaum R and Kufe D . (1999). Nature, 399, 814–817.
Zeng X, Lee H, Zhang Q and Lu H . (2001). J. Biol. Chem., 276, 48–52.
Zeng X, Li X, Miller A, Yuan Z, Yuan W, Kwok RP, Goodman R and Lu H . (2000). Mol. Cell. Biol., 20, 1299–1310.
Zhang Q, Yao H, Vo N and Goodman RH . (2000). Proc. Natl. Acad. Sci. USA, 97, 14323–14328.
Zhao R, Gish K, Murphy M, Yin Y, Notterman D, Hoffman WH, Tom E, Mack DH and Levine AJ . (2000). Genes Dev., 14, 981–993.
Zhu J, Jiang J, Zhou W and Chen X . (1998). Cancer Res., 58, 5061–5065.
Zhu J, Nozell S, Wang J, Jiang J, Zhou W and Chen X . (2001). Oncogene, 20, 4050–4057.
Acknowledgements
We thank B Vogelstein, M Kaghad and H Arakawa for generously providing plasmids. We also thank Frederique Fricsh for technical assistance.
This work was supported by National Institutes of Health grant R01 CA92236 (DL), and in part by Canadian Institutes of Health Research grants MOP-14109 and MOP-42429 (DL) and National Cancer Institute of Canada grants (XJY). In addition, D Liao received pilot project grants from Biomedical Research Support Program for Medical Schools awarded to the University of Florida College of Medicine by Howard Hughes Medical Institute.
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Zhao, L., Liu, Y., Bertos, N. et al. PCAF is a coactivator for p73-mediated transactivation. Oncogene 22, 8316–8329 (2003). https://doi.org/10.1038/sj.onc.1206916
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DOI: https://doi.org/10.1038/sj.onc.1206916
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