Transcriptional regulation by p53: one protein, many possibilities (2024)

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

    CAS PubMed Google Scholar

  • Prives C and Hall PA (1999) The p53 pathway. J. Pathol. 187: 112–126.

    Article CAS PubMed Google Scholar

  • Jeffrey PD, Gorina S and Pavletich NP (1995) Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 angstroms. Science 267: 1498–1502.

    Article CAS PubMed Google Scholar

  • Brooks CL and Gu W (2003) Ubiquitination, phosphorylation and acetylation: the molecular basis for p53 regulation. Curr. Opin. Cell Biol. 15: 164–171.

    Article CAS PubMed Google Scholar

  • Appella E and Anderson CW (2001) Post-translational modifications and activation of p53 by genotoxic stresses. Eur. J. Biochem. 268: 2764–2772.

    Article CAS PubMed Google Scholar

  • Erster S and Moll UM (2005) Stress-induced p53 runs a transcription-independent death program. Biochem. Biophys. Res. Commun. 331: 843–850.

    Article CAS PubMed Google Scholar

  • Ko LJ and Prives C (1996) p53: puzzle and paradigm. Genes Dev. 10: 1054–1072.

    Article CAS PubMed Google Scholar

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

    Article CAS PubMed PubMed Central Google Scholar

  • Zhao R, Gish K, Murphy M, Yin Y, Notterman D, Hoffman WH, Tom E, Mack DH and Levine AJ (2000) Analysis of p53-regulated gene expression patterns using oligonucleotide arrays. Genes Dev. 14: 981–993.

    Article CAS PubMed PubMed Central Google Scholar

  • Inga A, Storici F, Darden TA and Resnick MA (2002) Differential transactivation by the p53 transcription factor is highly dependent on p53 level and promoter target sequence. Mol. Cell. Biol. 22: 8612–8625.

    Article CAS PubMed PubMed Central Google Scholar

  • Tomso DJ, Inga A, Menendez D, Pittman GS, Campbell MR, Storici F, Bell DA and Resnick MA (2005) Functionally distinct polymorphic sequences in the human genome that are targets for p53 transactivation. Proc. Natl. Acad. Sci. USA 102: 6431–6436.

    Article CAS PubMed PubMed Central Google Scholar

  • Resnick MA, Tomso D, Inga A, Menendez D and Bell D (2005) Functional diversity in the gene network controlled by the master regulator p53 in humans. Cell Cycle 4: 1026–1029.

    Article CAS PubMed Google Scholar

  • Zheng X and Chen X (2001) Aquaporin 3, a glycerol and water transporter, is regulated by p73 of the p53 family. FEBS Lett. 489: 4–7.

    Article CAS PubMed Google Scholar

  • Johnson RA, Ince TA and Scotto KW (2001) Transcriptional repression by p53 through direct binding to a novel DNA element. J. Biol. Chem. 276: 27716–27720.

    Article CAS PubMed Google Scholar

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

    Article PubMed Google Scholar

  • Walter K, Warnecke G, Bowater R, Deppert W and Kim EL (2005) tumor suppressor p53 binds with high affinity to CTG. CAG trinucleotide repeats and induces topological alterations in mismatched duplexes. J. Biol. Chem. 280: 42497–42507.

    Article CAS PubMed Google Scholar

  • Resnick MA and Inga A (2003) Functional mutants of the sequence-specific transcription factor p53 and implications for master genes of diversity. Proc. Natl. Acad. Sci. USA 100: 9934–9939.

    Article CAS PubMed PubMed Central Google Scholar

  • Jayaraman L and Prives C (1999) Covalent and noncovalent modifiers of the p53 protein. Cell Mol. Life Sci. 55: 76–87.

    Article CAS PubMed Google Scholar

  • Kim E and Deppert W (2006) The versatile interactions of p53 with DNA: when flexibility serves specificity. Cell Death Differ. 13: 885–889.

    Article CAS PubMed Google Scholar

  • Liu Y and Kulesz-Martin MF (2006) Sliding into home: facilitated p53 search for targets by the basic DNA binding domain. Cell Death Differ. 13: 881–884.

    Article CAS PubMed Google Scholar

  • Cho Y, Gorina S, Jeffrey PD and Pavletich NP (1994) Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 265: 346–355.

    Article CAS PubMed Google Scholar

  • Klein C, Planker E, Diercks T, Kessler H, Kunkele KP, Lang K, Hansen S and Schwaiger M (2001) NMR spectroscopy reveals the solution dimerization interface of p53 core domains bound to their consensus DNA. J. Biol. Chem. 276: 49020–49027.

    Article CAS PubMed Google Scholar

  • Rippin TM, Freund SM, Veprintsev DB and Fersht AR (2002) Recognition of DNA by p53 core domain and location of intermolecular contacts of cooperative binding. J. Mol. Biol. 319: 351–358.

    Article CAS PubMed Google Scholar

  • McLure KG and Lee PW (1998) How p53 binds DNA as a tetramer. EMBO J. 17: 3342–3350.

    Article CAS PubMed PubMed Central Google Scholar

  • Data available at International Agency for Research on Cancer TP53, database R8, available at www.iarc.fr/p53.

  • Bullock AN, Henckel J, DeDecker BS, Johnson CM, Nikolova PV, Proctor MR, Lane DP and Fersht AR (1997) Thermodynamic stability of wild-type and mutant p53 core domain. Proc. Natl. Acad. Sci. USA 94: 14338–14342.

    Article CAS PubMed PubMed Central Google Scholar

  • Wong KB, DeDecker BS, Freund SM, Proctor MR, Bycroft M and Fersht AR (1999) Hot-spot mutants of p53 core domain evince characteristic local structural changes. Proc. Natl. Acad. Sci. USA 96: 8438–8442.

    Article CAS PubMed PubMed Central Google Scholar

  • Bullock AN, Henckel J and Fersht AR (2000) Quantitative analysis of residual folding and DNA binding in mutant p53 core domain: definition of mutant states for rescue in cancer therapy. Oncogene 19: 1245–1256.

    Article CAS PubMed Google Scholar

  • Butler JS and Loh SN (2003) Structure, function, and aggregation of the zinc-free form of the p53 DNA binding domain. Biochemistry 42: 2396–2403.

    Article CAS PubMed Google Scholar

  • Foster BA, Coffey HA, Morin MJ and Rastinejad F (1999) Pharmacological rescue of mutant p53 conformation and function. Science 286: 2507–2510.

    Article CAS PubMed Google Scholar

  • Hansen S, Hupp TR and Lane DP (1996) Allosteric regulation of the thermostability and DNA binding activity of human p53 by specific interacting proteins. CRC Cell Transformation Group. J. Biol. Chem. 271: 3917–3924.

    Article CAS PubMed Google Scholar

  • Friedlander P, Legros Y, Soussi T and Prives C (1996) Regulation of mutant p53 temperature-sensitive DNA binding. J. Biol. Chem 271: 25468–25478.

    Article CAS PubMed Google Scholar

  • Butler JS and Loh SN (2005) Kinetic partitioning during folding of the p53 DNA binding domain. J. Mol. Biol. 350: 906–918.

    Article CAS PubMed Google Scholar

  • Di Como CJ, Gaiddon C and Prives C (1999) p73 function is inhibited by tumor-derived p53 mutants in mammalian cells. Mol. Cell. Biol. 9: 1438–1449.

    Article 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 CAS PubMed PubMed Central Google Scholar

  • Bensaad K, Le Bras M, Unsal K, Strano S, Blandino G, Tominaga O, Rouillard D and Soussi T (2003) Change of conformation of the DNA-binding domain of p53 is the only key element for binding of and interference with p73. J. Biol. Chem. 278: 10546–10555.

    Article CAS PubMed Google Scholar

  • Marin MC, Jost CA, Brooks LA, Irwin MS, O'Nions J, Tidy JA, James N, McGregor JM, Harwood CA, Yulug IG, Vousden KH, Allday MJ, Gusterson B, Ikawa S, Hinds PW, Crook T and Kaelin Jr WG (2000) A common polymorphism acts as an intragenic modifier of mutant p53 behaviour. Nat. Genet. 25: 47–54.

    Article CAS PubMed Google Scholar

  • Lang GA, Iwakuma T, Suh YA, Liu G, Rao VA, Parant JM, Valentin-Vega YA, Terzian T, Caldwell LC, Strong LC, El-Naggar AK and Lozano G (2004) Gain of function of a p53 hot spot mutation in a mouse model of Li–Fraumeni syndrome. Cell 119: 861–872.

    Article CAS PubMed Google Scholar

  • Olive KP, Tuveson DA, Ruhe ZC, Yin B, Willis NA, Bronson RT, Crowley D and Jacks T (2004) Mutant p53 gain of function in two mouse models of Li–Fraumeni syndrome. Cell 119: 847–860.

    Article CAS PubMed Google Scholar

  • Chan WM, Siu WY, Lau A and Poon RY (2004) How many mutant p53 molecules are needed to inactivate a tetramer? Mol. Cell. Biol. 24: 3536–3551.

    Article CAS PubMed PubMed Central Google Scholar

  • Ljungman M, O'Hagan HM and Paulsen MT (2001) Induction of ser15 and lys382 modifications of p53 by blockage of transcription elongation. Oncogene 20: 5964–5971.

    Article CAS PubMed Google Scholar

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

    Article CAS PubMed PubMed Central Google Scholar

  • Rodriguez MS, Desterro JM, Lain S, Lane DP and Hay RT (2000) Multiple C-terminal lysine residues target p53 for ubiquitin-proteasome-mediated degradation. Mol. Cell. Biol. 20: 8458–8467.

    Article CAS PubMed PubMed Central Google Scholar

  • Xirodimas DP, Saville MK, Bourdon JC, Hay RT and Lane DP (2004) Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell 118: 83–97.

    Article CAS PubMed Google Scholar

  • Li M, Luo J, Brooks CL and Gu W (2002) Acetylation of p53 inhibits its ubiquitination by Mdm2. J. Biol. Chem. 277: 50607–50611.

    Article CAS PubMed Google Scholar

  • Chuikov S, Kurash JK, Wilson JR, Xiao B, Justin N, Ivanov GS, McKinney K, Tempst P, Prives C, Gamblin SJ, Barlev NA and Reinberg D (2004) Regulation of p53 activity through lysine methylation. Nature 432: 353–360.

    Article CAS PubMed Google Scholar

  • Muller S, Ledl A and Schmidt D (2004) SUMO: a regulator of gene expression and genome integrity. Oncogene 23: 1998–2008.

    Article CAS PubMed Google Scholar

  • Ahn J and Prives C (2001) The C-terminus of p53: the more you learn the less you know. Nat. Struct. Biol. 8: 730–732.

    Article CAS PubMed Google Scholar

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

    CAS PubMed Google Scholar

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

    CAS PubMed PubMed Central Google Scholar

  • Luo J, Li M, Tang Y, Laszkowska M, Roeder RG and Gu W (2004) Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo. Proc. Natl. Acad. Sci. USA 101: 2259–2264.

    Article CAS PubMed PubMed Central Google Scholar

  • Anderson ME, Woelker B, Reed M, Wang P and Tegtmeyer P (1997) Reciprocal interference between the sequence-specific core and nonspecific C-terminal DNA binding domains of p53: implications for regulation. Mol. Cell. Biol. 17: 6255–6264.

    Article CAS PubMed PubMed Central Google Scholar

  • Ayed A, Mulder FA, Yi GS, Lu Y, Kay LE and Arrowsmith CH (2001) Latent and active p53 are identical in conformation. Nat. Struct. Biol. 8: 756–760.

    Article CAS PubMed Google Scholar

  • Friedler A, Veprintsev DB, Freund SM, von Glos KI and Fersht AR (2005) Modulation of binding of DNA to the C-terminal domain of p53 by acetylation. Structure (Cambridge) 13: 629–636.

    Article CAS Google Scholar

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

    Article CAS PubMed Google Scholar

  • Kaeser MD and Iggo RD (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 CAS PubMed Google Scholar

  • Krummel KA, Lee CJ, Toledo F and Wahl GM (2005) The C-terminal lysines fine-tune P53 stress responses in a mouse model but are not required for stability control or transactivation. Proc. Natl. Acad. Sci. USA 102: 10188–10193.

    Article CAS PubMed PubMed Central Google Scholar

  • Feng L, Lin T, Uranishi H, Gu W and Xu Y (2005) Functional analysis of the roles of posttranslational modifications at the p53 C terminus in regulating p53 stability and activity. Mol. Cell Biol. 25: 5389–5395.

    Article CAS PubMed PubMed Central Google Scholar

  • McKinney K and Prives C (2002) Efficient specific DNA binding by p53 requires both its central and C-terminal domains as revealed by studies with high-mobility group 1 protein. Mol. Cell. Biol. 22: 6797–6808.

    Article CAS PubMed PubMed Central Google Scholar

  • Fojta M, Pivonkova H, Brazdova M, Nemcova K, Palecek J and Vojtesek B (2004) Investigations of the supercoil-selective DNA binding of wild type p53 suggest a novel mechanism for controlling p53 function. Eur. J. Biochem. 271: 3865–3876.

    Article CAS PubMed Google Scholar

  • Palecek E, Brazda V, Jagelska E, Pecinka P, Karlovska L and Brazdova M (2004) Enhancement of p53 sequence-specific binding by DNA supercoiling. Oncogene 23: 2119–2127.

    Article CAS PubMed Google Scholar

  • McKinney K, Mattia M, Gottifredi V and Prives C (2004) p53 linear diffusion along DNA requires its C terminus. Mol. Cell 16: 413–424.

    Article CAS PubMed Google Scholar

  • Liu Y, Lagowski JP, Vanderbeek GE and Kulesz-Martin MF (2004) Facilitated search for specific genomic targets by p53 C-terminal basic DNA binding domain. Cancer Biol. Ther. 3: 1102–1108.

    Article CAS PubMed Google Scholar

  • Harms KL and Chen X (2005) The C terminus of p53 family proteins is a cell fate determinant. Mol. Cell. Biol. 25: 2014–2030.

    Article CAS PubMed PubMed Central Google Scholar

  • Palecek E, Brazdova M, Cernocka H, Vlk D, Brazda V and Vojtesek B (1999) Effect of transition metals on binding of p53 protein to supercoiled DNA and to consensus sequence in DNA fragments. Oncogene 18: 3617–3625.

    Article CAS PubMed Google Scholar

  • Okorokov AL and Milner J (1999) An ATP/ADP-dependent molecular switch regulates the stability of p53-DNA complexes. Mol. Cell. Biol. 19: 7501–7510.

    Article CAS PubMed PubMed Central Google Scholar

  • McLure KG, Takagi M and Kastan MB (2004) NAD+ modulates p53 DNA binding specificity and function. Mol. Cell. Biol. 24: 9958–9967.

    Article CAS PubMed PubMed Central Google Scholar

  • Nagaich AK, Appella E and Harrington RE (1997) DNA bending is essential for the site-specific recognition of DNA response elements by the DNA binding domain of the tumor suppressor protein p53. J. Biol. Chem. 272: 14842–14849.

    Article CAS PubMed Google Scholar

  • Bell S, Klein C, Muller L, Hansen S and Buchner J (2002) p53 contains large unstructured regions in its native state. J. Mol. Biol. 322: 917–927.

    Article CAS PubMed Google Scholar

  • Dawson R, Muller L, Dehner A, Klein C, Kessler H and Buchner J (2003) The N-terminal domain of p53 is natively unfolded. J. Mol. Biol. 332: 1131–1141.

    Article CAS PubMed Google Scholar

  • Lee H, Mok KH, Muhandiram R, Park KH, Suk JE, Kim DH, Chang J, Sung YC, Choi KY and Han KH (2000) Local structural elements in the mostly unstructured transcriptional activation domain of human p53. J. Biol. Chem. 275: 29426–29432.

    Article CAS PubMed Google Scholar

  • Lin JY, Chen JD, Elenbaas B and Levine AJ (1994) Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Gene Dev. 8: 1235–1246.

    Article CAS PubMed Google Scholar

  • Candau R, Scolnick DM, Darpino P, Ying CY, Halazonetis TD and Berger SL (1997) Two tandem and independent sub-activation domains in the amino terminus of p53 require the adaptor complex for activity. Oncogene 15: 807–816.

    Article CAS PubMed Google Scholar

  • Chang J, Kim DH, Lee SW, Choi KY and Sung YC (1995) Transactivation ability of p53 transcriptional activation domain is directly related to the binding affinity to TATA-binding protein. J. Biol. Chem. 270: 25014–25019.

    Article CAS PubMed Google Scholar

  • Zilfou JT, Hoffman WH, Sank M, George DL and Murphy M (2001) The corepressor mSin3a interacts with the proline-rich domain of p53 and protects p53 from proteasome-mediated degradation. Mol. Cell. Biol. 21: 3974–3985.

    Article CAS PubMed PubMed Central Google Scholar

  • Zheng H, You H, Zhou XZ, Murray SA, Uchida T, Wulf G, Gu L, Tang X, Lu KP and Xiao ZX (2002) The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature 419: 849–853.

    Article CAS PubMed Google Scholar

  • Zacchi P, Gostissa M, Uchida T, Salvagno C, Avolio F, Volinia S, Ronai Z, Blandino G, Schneider C and Del Sal G (2002) The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults. Nature 419: 853–857.

    Article CAS PubMed Google Scholar

  • Dornan D, Shimizu H, Burch L, Smith AJ and Hupp TR (2003) The proline repeat domain of p53 binds directly to the transcriptional coactivator p300 and allosterically controls DNA-dependent acetylation of p53. Mol. Cell. Biol. 23: 8846–8861.

    Article CAS PubMed PubMed Central Google Scholar

  • Curtin JC and Spinella MJ (2005) p53 in human embryonal carcinoma: identification of a transferable, transcriptional repression domain in the N-terminal region of p53. Oncogene 24: 1481–1490.

    Article CAS PubMed Google Scholar

  • Bond GL, Hu W and Levine AJ (2005) MDM2 is a central node in the p53 pathway: 12 years and counting. Curr. Cancer Drug Targets 5: 3–8.

    Article CAS PubMed Google Scholar

  • Zhang Y and Xiong Y (2001) A p53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation. Science 292: 1910–1915.

    Article CAS PubMed Google Scholar

  • Shieh S-Y, Ikeda M, Taya Y and Prives C (1997) DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91: 325–334.

    Article CAS PubMed Google Scholar

  • Chehab NH, Malikzay A, Stavridi ES and Halazonetis TD (1999) Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc. Natl. Acad. Sci. USA 96: 13777–13782.

    Article CAS PubMed PubMed Central Google Scholar

  • Dumaz N and Meek DW (1999) Serine15 phosphorylation stimulates p53 transactivation but does not directly influence interaction with HDM2. EMBO J. 18: 7002–7010.

    Article CAS PubMed PubMed Central Google Scholar

  • Lambert PF, Kashanchi F, Radonovich MF, Shiekhattar R and Brady JN (1998) Phosphorylation of p53 serine 15 increases interaction with CBP. J. Biol. Chem. 273: 33048–33053.

    CAS PubMed Google Scholar

  • Saito S, Goodarzi AA, Higashimoto Y, Noda Y, Lees-Miller SP, Appella E and Anderson CW (2002) ATM mediates phosphorylation at multiple p53 sites, including Ser(46), in response to ionizing radiation. J. Biol. Chem. 277: 12491–12494.

    Article CAS PubMed Google Scholar

  • Mayo LD, Seo YR, Jackson MW, Smith ML, Rivera Guzman J, Korgaonkar CK and Donner DB (2005) Phosphorylation of human p53 at serine 46 determines promoter selection and whether apoptosis is attenuated or amplified. J. Biol. Chem. 280: 25953–25959.

    Article CAS PubMed Google Scholar

  • Saito S, Yamaguchi H, Higashimoto Y, Chao C, Xu Y, Fornace Jr AJ, Appella E and Anderson CW (2003) Phosphorylation site interdependence of human p53 post-translational modifications in response to stress. J. Biol. Chem. 278: 37536–37544.

    Article CAS PubMed Google Scholar

  • Ashcroft M, Kubbutat MH and Vousden KH (1999) Regulation of p53 function and stability by phosphorylation. Mol. Cell Biol. 19: 1751–1758.

    Article CAS PubMed PubMed Central Google Scholar

  • Thompson T, Tovar C, Yang H, Carvajal D, Vu BT, Xu Q, Wahl GM, Heimbrook DC and Vassilev LT (2004) Phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis. J. Biol. Chem. 279: 53015–53022.

    Article CAS PubMed Google Scholar

  • Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS, 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 CAS PubMed Google Scholar

  • Lee D, Kim JW, Seo T, Hwang SG, Choi EJ 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 CAS PubMed Google Scholar

  • Hill DA, de la Serna IL, Veal TM and Imbalzano AN (2004) BRCA1 interacts with dominant negative SWI/SNF enzymes without affecting hom*ologous recombination or radiation-induced gene activation of p21 or Mdm2. J. Cell Biochem. 91: 987–998.

    Article CAS PubMed Google Scholar

  • Hsu CH, Chang MD, Tai KY, Yang YT, Wang PS, Chen CJ, Wang YH, Lee SC, Wu CW and Juan LJ (2004) HCMV IE2-mediated inhibition of HAT activity downregulates p53 function. EMBO J. 23: 2269–2280.

    Article CAS PubMed PubMed Central Google Scholar

  • Barlev NA, Liu L, Chehab NH, Mansfield K, Harris KG, Halazonetis TD and Berger SL (2001) Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol. Cell 8: 1243–1254.

    Article CAS PubMed Google Scholar

  • Lill NL, Grossman SR, Ginsberg D, DeCaprio J and Livingston DM (1997) Binding and modulation of p53 by p300/CBP coactivators. Nature 387: 823–827.

    Article CAS PubMed Google Scholar

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

    Article CAS PubMed Google Scholar

  • An W, Kim J and Roeder RG (2004) Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53. Cell 117: 735–748.

    Article CAS PubMed Google Scholar

  • Gu W, Malik S, Ito M, Yuan CX, Fondell JD, Zhang X, Martinez E, Qin J and Roeder RG (1999) A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. Mol. Cell 3: 97–108.

    Article CAS PubMed Google Scholar

  • Zhang X, Krutchinsky A, f*ckuda A, Chen W, Yamamura S, Chait BT and Roeder RG (2005) MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription. Mol. Cell 19: 89–100.

    Article CAS PubMed Google Scholar

  • Xing J, Sheppard HM, Corneillie SI and Liu X (2001) p53 Stimulates TFIID-TFIIA-promoter complex assembly, and p53-T antigen complex inhibits TATA binding protein-TATA interaction. Mol. Cell Biol. 21: 3652–3661.

    Article CAS PubMed PubMed Central Google Scholar

  • Graunke DM, Fornace Jr AJ and Pieper RO (1999) Presetting of chromatin structure and transcription factor binding poise the human GADD45 gene for rapid transcriptional up-regulation. Nucleic Acids Res. 27: 3881–3890.

    Article CAS PubMed PubMed Central Google Scholar

  • Xiao G, White D and Bargonetti J (1998) p53 binds to a constitutively nucleosome free region of the mdm2 gene. Oncogene 16: 1171–1181.

    Article CAS PubMed Google Scholar

  • Braastad CD, Han Z and Hendrickson EA (2003) Constitutive DNase I hypersensitivity of p53-regulated promoters. J. Biol. Chem. 278: 8261–8268.

    Article CAS PubMed Google Scholar

  • Harms K, Nozell S and Chen X (2004) The common and distinct target genes of the p53 family transcription factors. Cell. Mol. Life Sci. 61: 822–842.

    Article CAS PubMed Google Scholar

  • Yu J and Zhang L (2005) The transcriptional targets of p53 in apoptosis control. Biochem. Biophys. Res. Commun. 331: 851–858.

    Article CAS PubMed Google Scholar

  • Mirza A, Wu Q, Wang L, McClanahan T, Bishop WR, Gheyas F, Ding W, Hutchins B, Hockenberry T, Kirschmeier P, Greene JR and Liu S (2003) Global transcriptional program of p53 target genes during the process of apoptosis and cell cycle progression. Oncogene 22: 3645–3654.

    Article CAS PubMed Google Scholar

  • Burns TF and El-Deiry WS (2003) Microarray analysis of p53 target gene expression patterns in the spleen and thymus in response to ionizing radiation. Cancer Biol. Ther. 2: 431–443.

    Article CAS PubMed Google Scholar

  • Sax JK, Stoddard A, Murphy ME, Chodosh L and El-Deiry WS (2003) Microarray expression profiling of p53-dependent transcriptional changes in an immortalized mouse embryo fibroblast cell line. Cancer Biol. Ther. 2: 416–430.

    Article CAS PubMed Google Scholar

  • Robinson M, Jiang P, Cui J, Li J, Wang Y, Swaroop M, Madore S, Lawrence TS and Sun Y (2003) Global genechip profiling to identify genes responsive to p53-induced growth arrest and apoptosis in human lung carcinoma cells. Cancer Biol. Ther. 2: 406–415.

    Article CAS PubMed Google Scholar

  • Zhu N, Gu L, Findley HW and Zhou M (2005) Transcriptional repression of the eukaryotic initiation factor 4E gene by wild type p53. Biochem. Biophys. Res. Commun. 335: 1272–1279.

    Article CAS PubMed Google Scholar

  • Kim E, Gunther W, Yoshizato K, Meissner H, Zapf S, Nusing RM, Yamamoto H, Van Meir EG, Deppert W and Giese A (2003) Tumor suppressor p53 inhibits transcriptional activation of invasion gene thromboxane synthase mediated by the proto-oncogenic factor ets-1. Oncogene 22: 7716–7727.

    Article CAS PubMed Google Scholar

  • Maiyar AC, Phu PT, Huang AJ and Firestone GL (1997) Repression of glucocorticoid receptor transactivation and DNA binding of a glucocorticoid response element within the serum/glucocorticoid-inducible protein kinase (sgk) gene promoter by the p53 tumor suppressor protein. Mol. Endocrinol. 11: 312–329.

    Article CAS PubMed Google Scholar

  • Liu G, Schwartz JA and Brooks SC (1999) p53 down-regulates ER-responsive genes by interfering with the binding of ER to ERE. Biochem. Biophys. Res. Commun. 264: 359–364.

    Article CAS PubMed Google Scholar

  • Maeda Y, Seidel SD, Wei G, Liu X and Sladek FM (2002) Repression of hepatocyte nuclear factor 4alpha tumor suppressor p53: involvement of the ligand-binding domain and histone deacetylase activity. Mol. Endocrinol. 16: 402–410.

    CAS PubMed Google Scholar

  • Gu L, Zhu N, Findley HW, Woods WG and Zhou M (2004) Identification and characterization of the IKKalpha promoter: positive and negative regulation by ETS-1 and p53, respectively. J. Biol. Chem. 279: 52141–52149.

    Article CAS PubMed Google Scholar

  • St Clair S, Giono L, Varmeh-Ziaie S, Resnick-Silverman L, Liu WJ, Padi A, Dastidar J, DaCosta A, Mattia M and Manfredi JJ (2004) DNA damage-induced downregulation of Cdc25C is mediated by p53 via two independent mechanisms: one involves direct binding to the cdc25C promoter. Mol. Cell 16: 725–736.

    Article PubMed Google Scholar

  • Ori A, Zauberman A, Doitsh G, Paran N, Oren M and Shaul Y (1998) p53 binds and represses the HBV enhancer: an adjacent enhancer element can reverse the transcription effect of p53. EMBO J. 17: 544–553.

    Article CAS PubMed PubMed Central Google Scholar

  • Lee KC, Crowe AJ and Barton MC (1999) p53-mediated repression of alpha-fetoprotein gene expression by specific DNA binding. Mol. Cell Biol. 19: 1279–1288.

    Article CAS PubMed PubMed Central Google Scholar

  • Li B and Lee MY (2001) Transcriptional regulation of the human DNA polymerase delta catalytic subunit gene POLD1 by p53 tumor suppressor and Sp1. J. Biol. Chem. 276: 29729–29739.

    Article CAS PubMed Google Scholar

  • Subbaramaiah K, Altorki N, Chung WJ, Mestre JR, Sampat A and Dannenberg AJ (1999) Inhibition of cyclooxygenase-2 gene expression by p53. J. Biol. Chem. 274: 10911–10915.

    Article CAS PubMed Google Scholar

  • Murphy M, Ahn J, Walker KK, Hoffman WH, Evans RM, Levine AJ and George DL (1999) Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. Genes Dev. 13: 2490–2501.

    Article CAS PubMed PubMed Central Google Scholar

  • Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M and Giaccia A (2001) Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol. Cell Biol. 21: 1297–1310.

    Article CAS PubMed PubMed Central Google Scholar

  • Ho JS, Ma W, Mao DY and Benchimol S (2005) p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest. Mol. Cell Biol. 25: 7423–7431.

    Article CAS PubMed PubMed Central Google Scholar

  • Johnson RA, Shepard EM and Scotto KW (2005) Differential regulation of MDR1 transcription by the p53 family members. Role of the DNA binding domain. J. Biol. Chem. 280: 13213–13219.

    Article CAS PubMed Google Scholar

  • Sengupta S, Shimamoto A, Koshiji M, Pedeux R, Rusin M, Spillare EA, Shen JC, Huang LE, Lindor NM, Furuichi Y and Harris CC (2005) Tumor suppressor p53 represses transcription of RECQ4 helicase. Oncogene 24: 1738–1748.

    Article CAS PubMed Google Scholar

  • Chun AC and Jin DY (2003) Transcriptional regulation of mitotic checkpoint gene MAD1 by p53. J. Biol. Chem. 278: 37439–37450.

    Article CAS PubMed Google Scholar

  • Wilkinson DS, Ogden SK, Stratton SA, Piechan JL, Nguyen TT, Smulian GA and Barton MC (2005) A direct intersection between p53 and transforming growth factor beta pathways targets chromatin modification and transcription repression of the alpha-fetoprotein gene. Mol. Cell Biol. 25: 1200–1212.

    Article CAS PubMed PubMed Central Google Scholar

  • Rocha S, Martin AM, Meek DW and Perkins ND (2003) p53 represses cyclin D1 transcription through down regulation of Bcl-3 and inducing increased association of the p52 NF-kappaB subunit with histone deacetylase 1. Mol. Cell Biol. 23: 4713–4727.

    Article CAS PubMed PubMed Central Google Scholar

  • Gottifredi V, Karni-Schmidt O, Shieh SS and Prives C (2001) p53 down-regulates CHK1 through p21 and the retinoblastoma protein. Mol. Cell Biol. 21: 1066–1076.

    Article CAS PubMed PubMed Central Google Scholar

  • Lohr K, Moritz C, Contente A and Dobbelstein M (2003) p21/CDKN1A mediates negative regulation of transcription by p53. J. Biol. Chem. 278: 32507–32516.

    Article CAS PubMed Google Scholar

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

    Article CAS PubMed Google Scholar

  • Venot C, Maratrat M, Dureuil C, Conseiller E, Bracco L and Debussche L (1998) The requirement for the p53 proline-rich functional domain for mediation of apoptosis is correlated with specific PIG3 gene transactivation and with transcriptional repression. EMBO J. 17: 4668–4679.

    Article CAS PubMed PubMed Central Google Scholar

  • Li J, Tan M, Li L, Pamarthy D, Lawrence TS and Sun Y (2005) SAK, a new polo-like kinase, is transcriptionally repressed by p53 and induces apoptosis upon RNAi silencing. Neoplasia 7: 312–323.

    Article CAS PubMed PubMed Central Google Scholar

  • Gridasova AA and Henry RW (2005) The p53 tumor suppressor protein represses human snRNA gene transcription by RNA polymerases II and III independently of sequence-specific DNA binding. Mol. Cell Biol. 25: 3247–3260.

    Article CAS PubMed PubMed Central Google Scholar

  • Zhai W and Comai L (2000) Repression of RNA polymerase I transcription by the tumor suppressor p53. Mol. Cell Biol. 20: 5930–5938.

    Article CAS PubMed PubMed Central Google Scholar

  • Budde A and Grummt I (1999) p53 represses ribosomal gene transcription. Oncogene 18: 1119–1124.

    Article CAS PubMed Google Scholar

  • Stein T, Crighton D, Warnock LJ, Milner J and White RJ (2002) Several regions of p53 are involved in repression of RNA polymerase III transcription. Oncogene 21: 5540–5547.

    Article CAS PubMed Google Scholar

  • Crighton D, Woiwode A, Zhang C, Mandavia N, Morton JP, Warnock LJ, Milner J, White RJ and Johnson DL (2003) p53 represses RNA polymerase III transcription by targeting TBP and inhibiting promoter occupancy by TFIIIB. EMBO J. 22: 2810–2820.

    Article CAS PubMed PubMed Central Google Scholar

  • Eichhorn K and Jackson SP (2001) A role for TAF3B2 in the repression of human RNA polymerase III transcription in nonproliferating cells. J. Biol. Chem. 276: 21158–21165.

    Article CAS PubMed Google Scholar

  • Cairns CA and White RJ (1998) p53 is a general repressor of RNA polymerase III transcription. EMBO J. 17: 3112–3123.

    Article CAS PubMed PubMed Central Google Scholar

  • Bourdon JC, Fernandes K, Murray-Zmijewski F, Liu G, Diot A, Xirodimas DP, Saville MK and Lane DP (2005) p53 isoforms can regulate p53 transcriptional activity. Genes Dev. 19: 2122–2137.

    Article CAS PubMed PubMed Central Google Scholar

  • Rohaly G, Chemnitz J, Dehde S, Nunez AM, Heukeshoven J, Deppert W and Dornreiter I (2005) A novel human p53 isoform is an essential element of the ATR-intra-S phase checkpoint. Cell 122: 21–32.

    Article CAS PubMed Google Scholar

  • Harms KL and Chen X (2006) The functional domains in p53 family proteins exhibit both common and distinct properties. Cell Death Differ. 13: 890–897.

    Article CAS PubMed Google Scholar

  • Transcriptional regulation by p53: one protein, many possibilities (2024)

    FAQs

    How does p53 regulate transcription? ›

    p53 regulates transcription via two functionally specialized transactivation domains. p53 recognizes its DNA response elements by an elaborate mechanism involving a sequence-specific core DNA-binding domain and the regulatory C-terminal domain.

    How many genes does p53 regulate? ›

    Arguably p53's most important function is to act as a transcription factor that directly regulates perhaps several hundred of the cell's RNA polymerase II (RNAP II)-transcribed genes, and indirectly regulates thousands of others. Indeed p53 is the most well studied mammalian transcription factor.

    What proteins regulate p53? ›

    The major negative regulator of p53 is the Mdm2 proto-oncogene. Mdm2 is transcriptionally induced by p53, thus p53 triggers its own destruction through a negative feedback loop. This feedback loop leads to oscillations in the expression of both proteins following DNA damage.

    What is the function of the p53 protein in cell cycle regulation? ›

    This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way. The p53 protein is located in the nucleus of cells throughout the body, where it attaches (binds) directly to DNA.

    What processes are regulated by p53? ›

    p53 also regulates many cellular processes including metabolism, antioxidant response, and DNA repair.

    What is translational regulation of p53? ›

    The translation of p53 mRNA is enhanced as a consequence of the RPL26 binding and IR stress. The underlying mechanism assumes that stress activates RPL26 and elevates its affinity to the 5′UTR of p53 mRNA. In turn, the interaction alters the distribution of the mRNA on polysomes and can enhance p53 translation [55].

    What cancers are associated with p53? ›

    Somatic Mutations. Somatic TP53 mutations occur in almost every type of cancer at rates from 38%–50% in ovarian, esophageal, colorectal, head and neck, larynx, and lung cancers to about 5% in primary leukemia, sarcoma, testicular cancer, malignant melanoma, and cervical cancer (Fig. 1).

    What does p53 positive mean? ›

    Marks et al. reported that p53 positivity was defined as a single malignant breast epithelial cell with positive nuclear staining for p53 (19). Martinazzi et al. reported that some nuclei with mutant p53 protein staining were considered positive (20).

    What does the p53 gene control? ›

    A gene that makes a protein that is found inside the nucleus of cells and plays a key role in controlling cell division and cell death. Mutations (changes) in the p53 gene may cause cancer cells to grow and spread in the body.

    How to increase p53 naturally? ›

    An antioxidant found in green tea may increase levels of p53, a natural anti-cancer protein, known as the "guardian of the genome" for its ability to repair DNA damage or destroy cancerous cells.

    Is p53 negative good or bad? ›

    Therefore, loss of functional p53, which renders cells unable to engage apoptosis or senescence programs after exposure to cellular stress, contributes to tumor formation. Indeed, TP53 mutation is associated with poor prognosis in many human tumors, including breast cancer (2). Figure 2.

    How to repair the p53 gene? ›

    Aminoglycosides to Rescue p53 Nonsense Mutations. Another interesting approach targeting p53 mutations is to rescue p53 nonsense mutations and restore wtp53 activity using aminoglycosides such as clinically available gentamicin.

    What is the life expectancy of a person with a TP53 mutation? ›

    However, there remains a small but challenging subgroup of patients who show ultra high-risk genetics (17p deletion, TP53 mutation) and/or poor response to chemoimmunotherapy. The median life expectancy of these patients is below 2 to 3 years with standard regimens.

    What is the primary function of the p53 protein? ›

    The p53 gene like the Rb gene, is a tumor suppressor gene, i.e., its activity stops the formation of tumors. If a person inherits only one functional copy of the p53 gene from their parents, they are predisposed to cancer and usually develop several independent tumors in a variety of tissues in early adulthood.

    What phase does p53 regulate? ›

    In addition to controlling the G1/S checkpoint, p53 also has a role in regulating genes required for progression through G2 phase and mitosis. Cell cycle-dependent expression of these genes is controlled by CHR or CDE/CHR sites in their promoters31, 33 (Figure 1).

    What is the role of up-regulation of p53 transcription? ›

    Summary. p53 induces the transcription of genes that negatively regulate progression of the cell cycle in response to DNA damage or other cellular stressors and thus participates in maintaining genome stability. Under stress conditions, p53 must be activated to prohibit the replication of cells containing damaged DNA.

    How does p53 regulate DNA repair? ›

    p53 halts the cell cycle when DNA damage is detected, giving repair machineries time to act. It has also been directly implicated in DNA-repair pathways (e.g., remodeling chromatin during nucleotide excision repair).

    What is the mechanism of action of p53? ›

    p53 induces transcription of 14-3-3 sigma and represses the cell cycle protein-dependent kinase Cdc2. Gadd45 is a member of the growth arrest and DNA damage gene family. p53 regulates the transcription of Gadd45, disrupts the cyclin B1/Cdc2 complex, and further blocks the G2 phase.

    How does cell signaling regulate transcription? ›

    Hence, the signal amplification that results may lead to activation of an entire cellular pool of transcription factors. Thus, only cells that initiate the signaling cascade will alter expression, and they will do so with a maximal response, thereby generating a binary pattern of transcriptional regulation.

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