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The p53 Tumor Suppressor Pathway and Cancer pp 53–80Cite as

Transcriptional Activation by p53: Mechanisms and Targeted Genes

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Part of the book series: Protein Reviews ((PRON,volume 2))

Abstract

The best-characterized function of p53, the most renowned tumor suppressor, is that of transcriptional activation. Upon its first description as a regulator of gene expression, p53 was simply thought to bind to an element within the 5′ UTR of a target gene, which would lead to transcription, by the appropriate machinery within the cell. Over the past 10 years however, this process has proven to be much more complex and tightly regulated than originally visualized. From the posttranslational modifications and proteins associated with p53 to the choice of a subset of genes that p53 possesses the capability to activate, the regulation of p53 transcriptional activity exists on several levels. This review will focus on the alterations of p53 protein that control activity of the protein, how genomic binding sites for p53 are presently being found and then finally, how the p53 target gene group is growing and being clustered into subsets of gene families.

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References

  • Aprelikova, O., Pace, A. J., Fang, B., Koller, B. H., and Liu, E. T. (2001). BRCA1 is a selective co-activator of 14-3-3 sigma gene transcription in mouse embryonic stem cells. J Biol Chem 276:25647–25650.

    Article  PubMed  CAS  Google Scholar 

  • Aprelikova, O. N., Fang, B. S., Meissner, E. G., Cotter, S., Campbell, M., Kuthiala, A., Bessho, M., Jensen, R. A., and Liu, E. T. (1999). BRCA1-associated growth arrest is RB-dependent. Proc Natl Acad Sci USA 96:11866–11871.

    Article  PubMed  CAS  Google Scholar 

  • Ard, P. G., Chatterjee, C., Kunjibettu, S., Adside, L. R., Gralinski, L. E., and McMahon, S. B. (2002). Transcriptional regulation of the mdm2 oncogene by p53 requires TRRAP acetyltransferase complexes. Mol Cell Biol 22:5650–5661.

    Article  PubMed  CAS  Google Scholar 

  • Arizti, P., Fang, L., Park, I., Yin, Y., Solomon, E., Ouchi, T., Aaronson, S. A., and Lee, S.W. (2000). Tumor suppressor p53 is required to modulate BRCA1 expression. Mol Cell Biol 20:7450–7459.

    Article  PubMed  CAS  Google Scholar 

  • Avantaggiati, M. L., Ogryzko, V., Gardner, K., Giordano, A., Levine, A. S., and Kelly, K. (1997). Recruitment of p300/CBP in p53-dependent signal pathways. Cell 89:1175–1184.

    Article  PubMed  CAS  Google Scholar 

  • Barak, Y., Juven, T., Haffner, R., and Oren, M. (1993). mdm2 expression is induced by wild type p53 activity. EMBO J 12:461–468.

    PubMed  CAS  Google Scholar 

  • Bargonetti, J., Reynisdottir, I., Friedman, P. N., and Prives, C. (1992). Site-specific binding of wild-type p53 to cellular DNA is inhibited by SV40 T antigen and mutant p53. Genes Dev 6:1886–1898.

    Article  PubMed  CAS  Google Scholar 

  • Barlev, N. A., Liu, L., Chehab, N. H., Mansfield, K., Harris, K. G., Halazonetis, T. D., and Berger, S. L. (2001). Acetylation of p53 activates transcription through recruitment of co-activators/histone acetyltransferases. Mol Cell 8:1243–1254.

    Article  PubMed  CAS  Google Scholar 

  • Bennett, M., Macdonald, K., Chan, S. W., Luzio, J. P., Simari, R., and Weissberg, P. (1998). Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis. Science 282:290–293.

    Article  PubMed  CAS  Google Scholar 

  • Berger, S. L. (2002). Histone modifications in transcriptional regulation. Curr Opin Genet Dev 12:142–148.

    Article  PubMed  CAS  Google Scholar 

  • Bochar, D. A., Wang, L., Beniya, H., Kinev, A., Xue, Y., Lane, W. S., Wang, W., Kashanchi, F., and Shiekhattar, R. (2000). BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin remodeling to breast cancer. Cell 102:257–265.

    Article  PubMed  CAS  Google Scholar 

  • Boddy, M. N., Howe, K., Etkin, L. D., Solomon, E., and Freemont, P. S. (1996). PIC 1, a novel ubiquitinlike protein which interacts with the PML component of a multiprotein complex that is disrupted in acute promyelocytic leukaemia. Oncogene 13:971–982.

    PubMed  CAS  Google Scholar 

  • Breiding, D. E., Sverdrup, F., Grossel, M. J., Moscufo, N., Boonchai, W., and Androphy, E. J. (1997). Functional interaction of a novel cellular protein with the papillomavirus E2 transactivation domain. Mol Cell Biol 17:7208–7219.

    PubMed  CAS  Google Scholar 

  • Brown, C. E., Howe, L., Sousa, K., Alley, S. C., Carrozza, M. J., Tan, S., and Workman, J. L. (2001). Recruitment of HAT complexes by direct activator interactions with the ATM-related Tra1 subunit. Science 292:2333–2337.

    Article  PubMed  CAS  Google Scholar 

  • Brownell, J. E., Zhou, J., Ranalli, T., Kobayashi, R., Edmondson, D. G., Roth, S. Y., and Allis, C. D. (1996). Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84:843–851.

    Article  PubMed  CAS  Google Scholar 

  • Bulavin, D. V., Saito, S., Hollander, M. C., Sakaguchi, K., Anderson, C. W., Appella, E., and Fornace, A. J., Jr. (1999). Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. EMBO J 18:6845–6854.

    Article  PubMed  CAS  Google Scholar 

  • Burns, T. F., Fei, P., Scata, K. A., Dicker, D. T. and el-Deiry, W. S. (2003): Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic catastrophe in paclitaxel (taxol)-exposed cells. Mol Cell Biol 23:5556–5571.

    Article  PubMed  CAS  Google Scholar 

  • Bykov, V. J., Issaeva, N., Shilov, A., Hultcrantz, M., Pugacheva, E., Chumakov, P., Bergman, J., Wiman, K. G., and Selivanova, G. (2002). Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med 8:282–288.

    Article  PubMed  CAS  Google Scholar 

  • Caelles, C., Helmberg, A., and Karin, M. (1994). p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature 370:220–223.

    Article  PubMed  CAS  Google Scholar 

  • Chai, Y. L., Cui, J., Shao, N., Shyam, E., Reddy, P., and Rao, V. N. (1999). The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter. Oncogene 18:263–268.

    Article  PubMed  CAS  Google Scholar 

  • Chen, X., Ko, L. J., Jayaraman, L., and Prives, C. (1996). p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 10:2438–2451.

    Article  PubMed  CAS  Google Scholar 

  • Chin, K. V., Ueda, K., Pastan, I., and Gottesman, M. M. (1992). Modulation of activity of the promoter of the human MDR1 gene by Ras and p53. Science 255:459–462.

    Article  PubMed  CAS  Google Scholar 

  • Chu, G., and Chang, E. (1988). Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA. Science 242:564–567.

    Article  PubMed  CAS  Google Scholar 

  • Contente, A., Dittmer, A., Koch, M. C., Roth, J., and Dobbelstein, M. (2002). A polymorphic microsatellite that mediates induction of PIG3 by p53. Nat Genet 30:315–320.

    Article  PubMed  Google Scholar 

  • Costanzo, A., Merlo, P., Pediconi, N., Fulco, M., Sartorelli, V., Cole, P. A., Fontemaggi, G., Fanciulli, M., Schiltz, L., Blandino, G., et al. (2002). DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes. Mol Cell 9:175–186.

    Article  PubMed  CAS  Google Scholar 

  • Davison, T. S., Vagner, C., Kaghad, M., Ayed, A., Caput, D., and Arrowsmith, C. H. (1999). p73 and p63 are homotetramers capable of weak heterotypic interactions with each other but not with p53. J Biol Chem 274:18709–18714.

    Article  PubMed  CAS  Google Scholar 

  • DeLeo, A. B., Jay, G., Appella, E., Dubois, G. C., Law, L. W., and Old, L. J. (1979). Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc Natl Acad Sci USA 76:2420–2424.

    Article  PubMed  CAS  Google Scholar 

  • Demonacos, C., Krstic-Demonacos, M., and La Thangue, N. B. (2001). A TPR motif cofactor contributes to p300 activity in the p53 response. Mol Cell 8:71–84.

    Article  PubMed  CAS  Google Scholar 

  • Di Como, C. J., Gaiddon, C., and Prives, C. (1999). p73 function is inhibited by tumor-derived p53 mutants in mammalian cells. Mol Cell Biol 19:1438–1449.

    PubMed  Google Scholar 

  • D’Orazi, G., Cecchinelli, B., Bruno, T., Manni, I., Higashimoto, Y., Saito, S., Gostissa, M., Coen, S., Marchetti, A., Del Sal, G., et al. (2002). Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis. Nat Cell Biol 4:11–19.

    Article  PubMed  CAS  Google Scholar 

  • El-Deiry, W. S. (1998). Regulation of p53 downstream genes, Semin Cancer Biol 8:345–357.

    Article  PubMed  CAS  Google Scholar 

  • El-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W., and Vogelstein, B. (1992). Definition of a consensus binding site for p53. Nat Genet 1:45–49.

    Article  PubMed  CAS  Google Scholar 

  • El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K.W., and Vogelstein, B. (1993). WAF1, a potential mediator of p53 tumor suppression. Cell 75:817–825.

    Article  PubMed  CAS  Google Scholar 

  • Espinosa, J. M., and Emerson, B. M. (2001). Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment. Mol Cell 8:57–69.

    Article  PubMed  CAS  Google Scholar 

  • Farmer, G., Bargonetti, J., Zhu, H., Friedman, P., Prywes, R., and Prives, C. (1992). Wild-type p53 activates transcription in vitro. Nature 358:83–86.

    Article  PubMed  CAS  Google Scholar 

  • Flores, E. R., Tsai, K. Y., Crowley, D., Sengupta, S., Yang, A., McKeon, F., and Jacks, T. (2002). p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature 416:560–564.

    Article  PubMed  CAS  Google Scholar 

  • Foster, B. A., Coffey, H. A., Morin, M. J., and Rastinejad, F. (1999). Pharmacological rescue of mutant p53 conformation and function, Science 286:2507–2510.

    Article  PubMed  CAS  Google Scholar 

  • Friborg, J., Jr., Kong, W., Hottiger, M. O., and Nabel, G. J. (1999). p53 inhibition by the LANA protein of KSHV protects against cell death. Nature 402:889–894.

    PubMed  CAS  Google Scholar 

  • Gaiddon, C., Lokshin, M., Ahn, J., Zhang, T., and Prives, C. (2001). A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain. Mol Cell Biol 21:1874–1887.

    Article  PubMed  CAS  Google Scholar 

  • Garkavtsev, I., Grigorian, I. A., Ossovskaya, V. S., Chernov, M. V., Chumakov, P. M., and Gudkov, A. V. (1998). The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control. Nature 391:295–298.

    Article  PubMed  CAS  Google Scholar 

  • Garkavtsev, I. V., Kley, N., Grigorian, I. A., and Gudkov, A. V. (2001). The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control. Oncogene 20:8276–8280.

    Article  PubMed  CAS  Google Scholar 

  • Gohler, T., Reimann, M., Cherny, D., Walter, K., Warnecke, G., Kim, E., and Deppert, W. (2002). Specific interaction of p53 with target binding sites is determined by DNA conformation and is regulated by the C-terminal domain. J Biol Chem 8:8.

    Google Scholar 

  • Gottifredi, V., Shieh, S., Taya, Y., and Prives, C. (2001). From the Cover: p53 accumulates but is functionally impaired when DNA synthesis is blocked. Proc Natl Acad Sci USA 98:1036–1041.

    Article  PubMed  CAS  Google Scholar 

  • Grigorian, M., Andresen, S., Tulchinsky, E., Kriajevska, M., Carlberg, C., Kruse, C., Cohn, M., Ambartsumian, N., Christensen, A., Selivanova, G., and Lukanidin, E. (2001). Tumor suppressor p53 protein is a new target for the metastasis-associated Mts1/S100A4 protein: functional consequences of their interaction. J Biol Chem 276:22699–22708.

    Article  PubMed  CAS  Google Scholar 

  • Gu, W., and Roeder, R. G. (1997). Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90:595–606.

    Article  PubMed  CAS  Google Scholar 

  • Gupta, S., Radha, V., Furukawa, Y., and Swarup, G. (2001). Direct transcriptional activation of human caspase-1 by tumor suppressor p53. J Biol Chem 276:10585–10588.

    Article  PubMed  CAS  Google Scholar 

  • Haas-Kogan, D., Shalev, N., Wong, M., Mills, G., Yount, G., and Stokoe, D. (1998). Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC. Curr Biol 8:1195–1198.

    Article  PubMed  CAS  Google Scholar 

  • Han, X., Patters, A. B., and Chesney, R. W. (2002). Transcriptional repression of taurine transporter gene (TauT) by p53 in renal cells. J Biol Chem 5:5.

    Google Scholar 

  • Haupt, Y., Rowan, S., Shaulian, E., Vousden, K. H., and Oren, M. (1995). Induction of apoptosis in HeLa cells by trans-activation-deficient p53. Genes Dev 9:2170–2183.

    Article  PubMed  CAS  Google Scholar 

  • Hermeking, H., Lengauer, C., Polyak, K., He, T. C., Zhang, L., Thiagalingam, S., Kinzler, K. W., and Vogelstein, B. (1997). 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression. Mol Cell 1:3–11.

    Article  PubMed  CAS  Google Scholar 

  • Hoffman, W. H., Biade, S., Zilfou, J. T., Chen, J., and Murphy, M. (2002). Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem 277:3247–3257.

    Article  PubMed  CAS  Google Scholar 

  • Hofmann, T. G., Moller, A., Sirma, H., Zentgraf, H., Taya, Y., Droge, W., Will, H., and Schmitz, M. L. (2002). Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nat Cell Biol 4:1–10.

    Article  PubMed  CAS  Google Scholar 

  • Hoh, J., Jin, S., Parrado, T., Edington, J., Levine, A. J., and Ott, J. (2002). The p53MH algorithm and its application in detecting p53-responsive genes. Proc Natl Acad Sci USA 99:8467–8472.

    Article  PubMed  CAS  Google Scholar 

  • Hollander, M. C., Sheikh, M. S., Bulavin, D. V., Lundgren, K., Augeri-Henmueller, L., Shehee, R., Molinaro, T. A., Kim, K. E., Tolosa, E., Ashwell, J. D., et al. (1999). Genomic instability in Gadd45a-deficient mice. Nat Genet 23:176–184.

    Article  PubMed  CAS  Google Scholar 

  • Ito, A., Lai, C. H., Zhao, X., Saito, S., Hamilton, M. H., Appella, E., and Yao, T. P. (2001). p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2. EMBO J 20:1331–1340.

    Article  PubMed  CAS  Google Scholar 

  • Iwabuchi, K., Bartel, P. L., Li, B., Marraccino, R., and Fields, S. (1994). Two cellular proteins that bind to wild-type but not mutant p53. Proc Natl Acad Sci USA 91:6098–6102.

    Article  PubMed  CAS  Google Scholar 

  • Iwabuchi, K., Li, B., Massa, H. F., Trask, B. J., Date, T., and Fields, S. (1998). Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2. J Biol Chem 273:26061–26068.

    Article  PubMed  CAS  Google Scholar 

  • Jenkins, J. R., Rudge, K., and Currie, G. A. (1984). Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature 312:651–654.

    Article  PubMed  CAS  Google Scholar 

  • Jin, Y., Zeng, S. X., Dai, M.-S., Yang, X.-J., and Lu, H. (2002). MDM2 Inhibits PCAF-mediated p53 acetylation. J Biol Chem. 279:20035–20043.

    Article  CAS  Google Scholar 

  • Johnson, R. A., Ince, T. A., and Scotto, K. W. (2001). Transcriptional repression by p53 through direct binding to a novel DNA element. J Biol Chem 276:27716–27720.

    Article  PubMed  CAS  Google Scholar 

  • Juan, L. J., Shia, W. J., Chen, M. H., Yang, W. M., Seto, E., Lin, Y. S., and Wu, C.W. (2000). Histone deacetylases specifically down-regulate p53-dependent gene activation. J Biol Chem 275:20436–20443.

    Article  PubMed  CAS  Google Scholar 

  • Kaeser, M. D., and Iggo, R. D. (2002). Chromatin immunoprecipitation analysis fails to support the latency model for regulation of p53 DNA binding activity in vivo. Proc Natl Acad Sci USA 99:95–100.

    Article  PubMed  CAS  Google Scholar 

  • Kaghad, M., Bonnet, H., Yang, A., Creancier, L., Biscan, J. C., Valent, A., Minty, A., Chalon, P., Lelias, J. M., Dumont, X., et al. (1997). Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90:809–819.

    Article  PubMed  CAS  Google Scholar 

  • Kahyo, T., Nishida, T., and Yasuda, H. (2001). Involvement of PIAS1 in the sumoylation of tumor suppressor p53. Mol Cell 8:713–718.

    Article  PubMed  CAS  Google Scholar 

  • Kamitani, T., Nguyen, H. P., and Yeh, E. T. (1997). Preferential modification of nuclear proteins by a novel ubiquitin-like molecule. J Biol Chem 272:14001–14004.

    Article  PubMed  CAS  Google Scholar 

  • Kim, E. J., Park, J. S., and Um, S. J. (2002). Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo. J Biol Chem 29:29.

    Google Scholar 

  • Kuo, M. H., and Allis, C. D. (1999). In vivo cross-linking and immunoprecipitation for studying dynamic protein:DNA associations in a chromatin environment. Methods 19:425–433.

    Article  PubMed  CAS  Google Scholar 

  • Lane, D. P. (1984). Cell immortalization and transformation by the p53 gene. Nature 312:596–597.

    Article  PubMed  CAS  Google Scholar 

  • Langley, E., Pearson, M., Faretta, M., Bauer, U. M., Frye, R. A., Minucci, S., Pelicci, P. G., and Kouzarides, T. (2002). Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 21:2383–2396.

    Article  PubMed  CAS  Google Scholar 

  • Lee, D., Kim, J. W., Seo, T., Hwang, S. G., Choi, E. J., and Choe, J. (2002). SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription. J Biol Chem 277:22330–22337.

    Article  PubMed  CAS  Google Scholar 

  • Lee, G. W., Melchior, F., Matunis, M. J., Mahajan, R., Tian, Q., and Anderson, P. (1998). Modification of Ran GTPase-activating protein by the small ubiquitin-related modifier SUMO-1 requires Ubc9, an E2-type ubiquitin-conjugating enzyme homologue. J Biol Chem 273:6503–6507.

    Article  PubMed  CAS  Google Scholar 

  • Lee, K. C., Crowe, A. J., and Barton, M. C. (1999). p53-mediated repression of alpha-fetoprotein gene expression by specific DNA binding. Mol Cell Biol 19:1279–1288.

    PubMed  CAS  Google Scholar 

  • Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., and Wang, X. (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–489.

    Article  PubMed  CAS  Google Scholar 

  • Lill, N. L., Grossman, S. R., Ginsberg, D., DeCaprio, J., and Livingston, D. M. (1997). Binding and modulation of p53 by p300/CBP co-activators. Nature 387:823–827.

    Article  PubMed  CAS  Google Scholar 

  • Lin, J., Blake, M., Tang, C., Zimmer, D., Rustandi, R. R., Weber, D. J., and Carrier, F. (2001). Inhibition of p53 transcriptional activity by the S100B calcium-binding protein. J Biol Chem 276:35037–35041.

    Article  PubMed  CAS  Google Scholar 

  • Lin, Y., Ma, W., and Benchimol, S. (2000). Pidd, a new death-domain-containing protein, is induced by p53 and promotes apoptosis. Nat Genet 26:122–127.

    Article  PubMed  CAS  Google Scholar 

  • Liu, L., Scolnick, D. M., Trievel, R. C., Zhang, H. B., Marmorstein, R., Halazonetis, T. D., and Berger, S. L. (1999). p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage. Mol Cell Biol 19:1202–1209.

    PubMed  CAS  Google Scholar 

  • Liu, Y., Colosimo, A. L., Yang, X. J., and Liao, D. (2000). Adenovirus E1B 55-kilodalton oncoprotein inhibits p53 acetylation by PCAF. Mol Cell Biol 20:5540–5553.

    Article  PubMed  CAS  Google Scholar 

  • Luo, J., Nikolaev, A. Y., Imai, S., Chen, D., Su, F., Shiloh, A., Guarente, L., and Gu, W. (2001). Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107:137–148.

    Article  PubMed  CAS  Google Scholar 

  • Luo, J., Su, F., Chen, D., Shiloh, A., and Gu, W. (2000). Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 408:377–381.

    Article  PubMed  CAS  Google Scholar 

  • MacLachlan, T. K., Dash, B. C., Dicker, D. T., and el-Deiry, W. S. (2000a). Repression of BRCA1 through a feedback loop involving p53. J Biol Chem 275:31869–31875.

    Article  PubMed  CAS  Google Scholar 

  • MacLachlan, T. K., and el-Deiry, W. S. (2002). Apoptotic threshold is lowered by p53 transactivation of caspase-6. Proc Natl Acad Sci USA 99:9492–9497.

    Article  PubMed  CAS  Google Scholar 

  • MacLachlan, T. K., Somasundaram, K., Sgagias, M., Shifman, Y., Muschel, R. J., Cowan, K. H., and el-Deiry, W. S. (2000b). BRCA1 effects on the cell cycle and the DNA damage response are linked to altered gene expression. J Biol Chem 275:2777–2785.

    Article  PubMed  CAS  Google Scholar 

  • MacLachlan, T. K., Takimoto, R., and el-Deiry, W. S. (2002). BRCA1 directs a selective p53-dependent transcriptional response towards growth arrest and DNA repair targets. Mol Cell Biol 22:4280–4292.

    Article  PubMed  CAS  Google Scholar 

  • Maehama, T., and Dixon, J. E. (1998). The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273:13375–13378.

    Article  PubMed  CAS  Google Scholar 

  • Mahajan, R., Delphin, C., Guan, T., Gerace, L., and Melchior, F. (1997). A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell 88:97–107.

    Article  PubMed  CAS  Google Scholar 

  • Matunis, M. J., Coutavas, E., and Blobel, G. (1996). A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex. J Cell Biol 135:1457–1470.

    Article  PubMed  CAS  Google Scholar 

  • Megidish, T., Xu, J. H., and Xu, C. W. (2002). Activation of p53 by protein inhibitor of activated Stat1 (PIAS1). J Biol Chem 277:8255–8259.

    Article  PubMed  CAS  Google Scholar 

  • Miyashita, T., Harigai, M., Hanada, M., and Reed, J. C. (1994). Identification of a p53-dependent negative response element in the bcl-2 gene. Cancer Res 54:3131–3135.

    PubMed  CAS  Google Scholar 

  • Miyashita, T., and Reed, J. C. (1995). Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80:293–299.

    Article  PubMed  CAS  Google Scholar 

  • Moroni, M. C., Hickman, E. S., Denchi, E. L., Caprara, G., Colli, E., Cecconi, F., Muller, H., and Helin, K. (2001). Apaf-1 is a transcriptional target for E2F and p53. Nat Cell Biol 3:552–558.

    Article  PubMed  CAS  Google Scholar 

  • Murphy, M., Ahn, J., Walker, K. K., Hoffman, W. H., Evans, R. M., Levine, A. J., and George, D. L. (1999). Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. Genes Dev 13:2490–2501.

    Article  PubMed  CAS  Google Scholar 

  • Murphy, M., Hinman, A., and Levine, A. J. (1996). Wild-type p53 negatively regulates the expression of a microtubule—associated protein. Genes Dev 10:2971–2980.

    Article  PubMed  CAS  Google Scholar 

  • Nagashima, M., Shiseki, M., Miura, K., Hagiwara, K., Linke, S. P., Pedeux, R., Wang, X. W., Yokota, J., Riabowol, K., and Harris, C. C. (2001). DNA damage-inducible gene p33ING2 negatively regulates cell proliferation through acetylation of p53. Proc Natl Acad Sci USA 98:9671–9676.

    Article  PubMed  CAS  Google Scholar 

  • Nakamura, S., Roth, J. A., and Mukhopadhyay, T. (2000). Multiple lysine mutations in the C-terminal domain of p53 interfere with MDM2-dependent protein degradation and ubiquitination. Mol Cell Biol 20:9391–9398.

    Article  PubMed  CAS  Google Scholar 

  • Nakano, K., and Vousden, K. H. (2001). PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell 7:683–694.

    Article  PubMed  CAS  Google Scholar 

  • Nal, B., Mohr, E., and Ferrier, P. (2001). Location analysis of DNA-bound proteins at the whole-genome level: untangling transcriptional regulatory networks. Bioessays 23:473–476.

    Article  PubMed  CAS  Google Scholar 

  • Nie, Y., Li, H. H., Bula, C. M., and Liu, X. (2000). Stimulation of p53 DNA binding by c-Abl requires the p53 C terminus and tetramerization. Mol Cell Biol 20:741–748.

    Article  PubMed  CAS  Google Scholar 

  • Oda, E., Ohki, R., Murasawa, H., Nemoto, J., Shibue, T., Yamashita, T., Tokino, T., Taniguchi, T., and Tanaka, N. (2000a). Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288:1053–1058.

    Article  PubMed  CAS  Google Scholar 

  • Oda, K., Arakawa, H., Tanaka, T., Matsuda, K., Tanikawa, C., Mori, T., Nishimori, H., Tamai, K., Tokino, T., Nakamura, Y., and Taya, Y. (2000b). p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell 102:849–862.

    Article  PubMed  CAS  Google Scholar 

  • Ogryzko, V. V., Schiltz, R. L., Russanova, V., Howard, B. H., and Nakatani, Y. (1996). The transcriptional coactivators p300 and CBP are histone acetyltransferases Cell 87:953–959.

    Article  PubMed  CAS  Google Scholar 

  • Ohki, R., Nemoto, J., Murasawa, H., Oda, E., Inazawa, J., Tanaka, N., and Taniguchi, T. (2000). Reprimo, a new candidate mediator of the p53-mediated cell cycle arrest at the G2 phase. J Biol Chem 275:22627–22630.

    Article  PubMed  CAS  Google Scholar 

  • Okamoto, K., and Beach, D. (1994). Cyclin Gis a transcriptional target of the p53 tumor suppressor protein. EMBO J 13:4816–4822.

    PubMed  CAS  Google Scholar 

  • Okamoto, K., Li, H., Jensen, M. R., Zhang, T., Taya, Y., Thorgeirsson, S. S., and Prives, C. (2002). Cyclin G recruits PP2A to dephosphorylate Mdm2. Mol Cell 9:761–771.

    Article  PubMed  CAS  Google Scholar 

  • Okamura, S., Arakawa, H., Tanaka, T., Nakanishi, H., Ng, C. C., Taya, Y., Monden, M., and Nakamura, Y. (2001). p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis. Mol Cell 8:85–94.

    Article  PubMed  CAS  Google Scholar 

  • Ouchi, T., Monteiro, A. N., August, A., Aaronson, S. A., and Hanafusa, H. (1998). BRCA1 regulates p53-dependent gene expression. Proc Natl Acad Sci USA 95:2302–2306.

    Article  PubMed  CAS  Google Scholar 

  • Pastorcic, M., and Das, H. K. (2000). Regulation of transcription of the human presenilin-1 gene by ets transcription factors and the p53 protooncogene. J Biol Chem 275:34938–34945.

    Article  PubMed  CAS  Google Scholar 

  • Pearson, M., Carbone, R., Sebastiani, C., Cioce, M., Fagioli, M., Saito, S., Higashimoto, Y., Appella, E., Minucci, S., Pandolfi, P. P., and Pelicci, P. G. (2000). PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature 406:207–210.

    Article  PubMed  CAS  Google Scholar 

  • Peng, Y. C., Breiding, D. E., Sverdrup, F., Richard, J., and Androphy, E. J. (2000). AMF-1/Gps2 binds p300 and enhances its interaction with papillomavirus E2 proteins. J Viroli 74:5872–5879.

    Article  CAS  Google Scholar 

  • Peng, Y. C., Kuo, F., Breiding, D. E., Wang, Y. F., Mansur, C. P., and Androphy, E. J. (2001). AMF1 (GPS2) modulates p53 transactivation. Mol Cell Biol 21:5913–5924.

    Article  PubMed  CAS  Google Scholar 

  • Prives, C., and Manley, J. L. (2001). Why is p53 acetylated?, Cell 107, 815–8.

    Article  PubMed  CAS  Google Scholar 

  • Ratovitski, E. A., Patturajan, M., Hibi, K., Trink, B., Yamaguchi, K., and Sidransky, D. (2001). p53 associates with and targets Delta Np63 into a protein degradation pathway. Proc Natl Acad Sci USA 98:1817–1822.

    Article  PubMed  CAS  Google Scholar 

  • Robertson, K. D., and Jones, P. A. (1998). The human ARF cell cycle regulatory gene promoter is a CpG island which can be silenced by DNA methylation and down-regulated by wild-type p53. Mol Cell Biol 18:6457–6473.

    PubMed  CAS  Google Scholar 

  • Robles, A. I., Bemmels, N. A., Foraker, A. B., and Harris, C. C. (2001). APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosis. Cancer Res 61:6660–6604.

    PubMed  CAS  Google Scholar 

  • Rodriguez, M. S., Desterro, J. M., Lain, S., Midgley, C. A., Lane, D. P., and Hay, R. T. (1999). SUMO-1 modification activates the transcriptional response of p53. EMBO J 18, 6455–6461.

    Article  PubMed  CAS  Google Scholar 

  • Rozenfeld-Granot, G., Krishnamurthy, J., Kannan, K., Toren, A., Amariglio, N., Givol, D., and Rechavi, G. (2002). A positive feedback mechanism in the transcriptional activation of Apaf-1 by p53 and the coactivator Zac-1. Oncogene 21:1469–1476.

    Article  PubMed  CAS  Google Scholar 

  • Sabbatini, P., and McCormick, F. (2002). MDMX Inhibits the p300/CBP-mediated acetylation of p53. DNA Cell Biol 21:519–525.

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi, K., Herrera, J. E., Saito, S., Miki, T., Bustin, M., Vassilev, A., Anderson, C. W., and Appella, E. (1998). DNA damage activates p53 through a phosphorylation-acetylation cascade. Genes Dev 12:2831–2841.

    PubMed  CAS  Google Scholar 

  • Sampath, J., Sun, D., Kidd, V. J., Grenet, J., Gandhi, A., Shapiro, L. H., Wang, Q., Zambetti, G. P., and Schuetz, J. D. (2001). Mutant p53 cooperates with ETS and selectively up-regulates human MDR1 not MRP1. J Biol Chem 276:39359–39367.

    Article  PubMed  CAS  Google Scholar 

  • Samuels-Lev, Y., O’Connor, D. J., Bergamaschi, D., Trigiante, G., Hsieh, J. K., Zhong, S., Campargue, I., Naumovski, L., Crook, T., and Lu, X. (2001). ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell 8:781–794.

    Article  PubMed  CAS  Google Scholar 

  • Sang, N., Avantaggiati, M. L., and Giordano, A. (1997). Roles of p300, pocket proteins, and hTBP in E1A-mediated transcriptional regulation and inhibition of p53 transactivation activity. J Cell Biochem 66:277–285.

    Article  PubMed  CAS  Google Scholar 

  • Sang, N., and Giordano, A. (1997). Extreme N terminus of E1A oncoprotein specifically associates with a new set of cellular proteins. J Cell Physiol 170:182–191.

    Article  PubMed  CAS  Google Scholar 

  • Sax, J. K., Fei, P., Murphy, M. E., Bernhard, E., Korsmeyer, S. J. and el-Deiry, W. S. (2002): BID regulation by p53 contributes to chemosensitivity. Nat Cell Biol. 4:842–849.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt, D., and Muller, S. (2002). Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity. Proc Natl Acad Sci USA 99:2872–2877.

    Article  PubMed  CAS  Google Scholar 

  • Schmieg, F. I., and Simmons, D. T. (1984). Intracellular location and kinetics of complex formation between simian virus 40 T antigen and cellular protein p53. J Virol 52 350–355.

    PubMed  CAS  Google Scholar 

  • Shen, Z., Pardington-Purtymun, P. E., Comeaux, J. C., Moyzis, R. K., and Chen, D. J. (1996). UBL1, a human ubiquitin-like protein associating with human RAD51/RAD52 proteins. Genomics 36:271–279.

    Article  PubMed  CAS  Google Scholar 

  • Sheppard, H. M., Corneillie, S. I., Espiritu, C., Gatti, A., and Liu, X. (1999). New insights into the mechanism of inhibition of p53 by simian virus 40 large T antigen. Mol Cell Biol 19:2746–2753.

    PubMed  CAS  Google Scholar 

  • Shikama, N., Lee, C. W., France, S., Delavaine, L., Lyon, J., Krstic-Demonacos, M., and La Thangue, N. B. (1999). A novel cofactor for p300 that regulates the p53 response. Mol Cell 4:365–376.

    Article  PubMed  CAS  Google Scholar 

  • Soengas, M. S., Alarcon, R. M., Yoshida, H., Giaccia, A. J., Hakem, R., Mak, T. W., and Lowe, S. W. (1999). Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science 284:156–159.

    Article  PubMed  CAS  Google Scholar 

  • Somasundaram, K., and el-Deiry, W. S. (1997). Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region. Oncogene 14:1047–1057.

    Article  PubMed  CAS  Google Scholar 

  • Somasundaram, K., MacLachlan, T. K., Burns, T. F., Sgagias, M., Cowan, K. H., Weber, B. L., and el-Deiry, W. S. (1999). BRCA1 signals ARF-dependent stabilization and coactivation of p53. Oncogene 18:6605–6614.

    Article  PubMed  CAS  Google Scholar 

  • Somasundaram, K., Zhang, H., Zeng, Y. X., Houvras, Y., Peng, Y., Wu, G. S., Licht, J. D., Weber, B. L., and el-Deiry, W. S. (1997). Arrest of the cell cycle by the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAF1/CiP1. Nature 389:187–190.

    Article  PubMed  CAS  Google Scholar 

  • Srinivasula, S. M., Ahmad, M., Fernandes-Alnemri, T., and Alnemri, E. S. (1998). Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization. Mol Cell 1:949–957.

    Article  PubMed  CAS  Google Scholar 

  • Stambolic, V., MacPherson, D., Sas, D., Lin, Y., Snow, B., Jang, Y., Benchimol, S., and Mak, T.W. (2001). Regulation of PTEN transcription by p53. Mol Cell 8:317–325.

    Article  PubMed  CAS  Google Scholar 

  • Stambolic, V., Suzuki, A., de la Pompa, J. L., Brothers, G. M., Mirtsos, C., Sasaki, T., Ruland, J., Penninger, J. M., Siderovski, D. P., and Mak, T. W. (1998). Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95:29–39.

    Article  PubMed  CAS  Google Scholar 

  • Strano, S., Munarriz, E., Rossi, M., Cristofanelli, B., Shaul, Y., Castagnoli, L., Levine, A. J., Sacchi, A., Cesareni, G., Oren, M., and Blandino, G. (2000). Physical and functional interaction between p53 mutants and different isoforms of p73. J Biol Chem 275:29503–29512.

    Article  PubMed  CAS  Google Scholar 

  • Szak, S. T., Mays, D., and Pietenpol, J. A. (2001). Kinetics of p53 binding to promoter sites in vivo. Mol Cell Biol 21:3375–3386.

    Article  PubMed  CAS  Google Scholar 

  • Takekawa, M., Adachi, M., Nakahata, A., Nakayama, I., Itoh, F., Tsukuda, H., Taya, Y., and Imai, K. (2000). p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. EMBO J 19:6517–6526.

    Article  PubMed  CAS  Google Scholar 

  • Takimoto, R., MacLachlan, T. K., Dicker, D. T., Niitsu, Y., Mori, T., and el-Deiry, W. S. (2002a). BRCA1 transcriptionally regulates damaged DNA binding protein (DDB2) in the DNA repair response following UV-irradiation. Cancer Biol Ther 1:177–186; discussion 187–188.

    PubMed  CAS  Google Scholar 

  • Takimoto, R., Wang, W., Dicker, D. T., Rastinejad, F., Lyssikatos, J., and el-Deiry, W. S. (2002b). The mutant p53-conformation modifying drug, CP-31398, can induce apoptosis of human cancer cells and can stabilize wild-type p53 protein. Cancer Biol Ther 1:47–55; discussion 56–57.

    PubMed  CAS  Google Scholar 

  • Tan, T., and Chu, G. (2002). p53 Binds and activates the xeroderma pigmentosum DDB2 gene in humans but not mice. Mol Cell Biol 22:3247–3254.

    Article  PubMed  CAS  Google Scholar 

  • Tanaka, H., Arakawa, H., Yamaguchi, T., Shiraishi, K., Fukuda, S., Matsui, K., Takei, Y., and Nakamura, Y. (2000). A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature 404:42–49.

    Article  PubMed  CAS  Google Scholar 

  • Tokino, T., Thiagalingam, S., el-Deiry, W. S., Waldman, T., Kinzler, K.W., and Vogelstein, B. (1994). p53 tagged sites from human genomic DNA. Hum Mol Genet 3:1537–1542.

    Article  PubMed  CAS  Google Scholar 

  • Vaziri, H., Dessain, S. K., Ng Eaton, E., Imai, S. I., Frye, R. A., Pandita, T. K., Guarente, L., and Weinberg, R. A. (2001). hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107:149–159.

    Article  PubMed  CAS  Google Scholar 

  • Vogelstein, B., Lane, D., and Levine, A. J. (2000). Surfing the p53 network. Nature 408:307–310.

    Article  PubMed  CAS  Google Scholar 

  • Vousden, K. H. (2002). Activation of the p53 tumor suppressor protein. Biochim Biophys Acta 1602:47–59.

    PubMed  CAS  Google Scholar 

  • Wagner, A. J., Kokontis, J. M., and Hay, N. (1994). Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1. Genes Dev 8:2817–2830.

    Article  PubMed  CAS  Google Scholar 

  • Wang, T., Kobayashi, T., Takimoto, R., Denes, A. E., Snyder, E. L., el-Deiry, W. S., and Brachmann, R. K. (2001). hADA3 is required for p53 activity. EMBO J 20:6404–6413.

    Article  PubMed  CAS  Google Scholar 

  • Xiao, G., Chicas, A., Olivier, M., Taya, Y., Tyagi, S., Kramer, F. R., and Bargonetti, J. (2000). A DNA damage signal is required for p53 to activate gadd45. Cancer Res 60:1711–1719.

    PubMed  CAS  Google Scholar 

  • Xu, D., Wilson, T. J., Chan, D., De Luca, E., Zhou, J., Hertzog, P. J., and Kola, I. (2002). Ets1 is required for p53 transcriptional activity in UV-induced apoptosis in embryonic stem cells. EMBO J 21:4081–4093.

    Article  PubMed  CAS  Google Scholar 

  • Xu, X., Qiao, W., Linke, S. P., Cao, L., Li, W. M., Furth, P. A., Harris, C. C., and Deng, C. X. (2001). Genetic interactions between tumor suppressors Brca1 and p53 in apoptosis, cell cycle and tumorigenesis. Nat Genet 28:266–271.

    Article  PubMed  CAS  Google Scholar 

  • Yan, C., Wang, H., and Boyd, D. D. (2002). ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter. J Biol Chem 277:10804–10812.

    Article  PubMed  CAS  Google Scholar 

  • Yang, A., Kaghad, M., Wang, Y., Gillett, E., Fleming, M. D., Dotsch, V., Andrews, N. C., Caput, D., and McKeon, F. (1998). p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 2:305–316.

    Article  PubMed  CAS  Google Scholar 

  • Yew, P. R., and Berk, A. J. (1992). Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein. Nature 357:82–85.

    Article  PubMed  CAS  Google Scholar 

  • Yu, J., Zhang, L., Hwang, P. M., Kinzler, K. W., and Vogelstein, B. (2001). PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell 7:673–682.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, H., Somasundaram, K., Peng, Y., Tian, H., Bi, D., Weber, B. L., and el-Deiry, W. S. (1998). BRCA1 physically associates with p53 and stimulates its transcriptional activity. Oncogene 16:1713–1721.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, Y., Ng, H. H., Erdjument-Bromage, H., Tempst, P., Bird, A., and Reinberg, D. (1999). Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev 13:1924–1935.

    Article  PubMed  CAS  Google Scholar 

  • Zheng, L., Pan, H., Li, S., Flesken-Nikitin, A., Chen, P. L., Boyer, T. G., and Lee, W. H. (2000). Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1. Mol Cell 6:757–768.

    Article  PubMed  CAS  Google Scholar 

  • Zhu, Q., Wani, G., Wani, M. A., and Wani, A. A. (2001). Human homologue of yeast Rad23 protein A interacts with p300/cyclic AMP-responsive element binding (CREB)-binding protein to down-regulate transcriptional activity of p53. Cancer Res 61:64–70.

    PubMed  CAS  Google Scholar 

  • Zou, H., Henzel, W. J., Liu, X., Lutschg, A., and Wang, X. (1997). Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90:405–413.

    Article  PubMed  CAS  Google Scholar 

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  1. Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Departments of Medicine, Genetics, and Pharmacology, and Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA

    Timothy MacLachlan & Wafik El-Deiry

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  1. St. Jude Children’s Research Hospital, Memphis, Tennessee

    Gerard P. Zambetti

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MacLachlan, T., El-Deiry, W. (2005). Transcriptional Activation by p53: Mechanisms and Targeted Genes. In: Zambetti, G.P. (eds) The p53 Tumor Suppressor Pathway and Cancer. Protein Reviews, vol 2. Springer, Boston, MA. https://doi.org/10.1007/0-387-30127-5_3

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