Abstract
The p53 tumor suppressor is a tetrameric transcription factor that is posttranslational modified at <20 different sites by phosphorylation, acetylation, or sumoylation in response to various cellular stress conditions. Specific posttranslational modifications, or groups of modifications, that result from the activation of different stress-induced signaling pathways are thought to modulate p53 activity to regulate cell fate by inducing cell cycle arrest, apoptosis, or cellular senescence. Here we review recent progress in characterizing the upstream signaling pathways whose activation in response to various genotoxic and nongenotoxic stresses result in p53 posttranslational modifications.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Abraham, R. T. (2001). Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 15:2177–2196.
Abraham, R. T. (2003). Checkpoint signaling: Epigenetic events sound the DNA strand-breaks alarm to the ATM protein kinase. Bioessays 25:627–630.
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.
Ahn, J., Urist, M., and Prives, C. (2003). Questioning the role of checkpoint kinase 2 in the p53 DNA damage response. J Biol Chem 278:20480–20489.
Ahn, J.-Y., Schwarz, J. K., Piwnica-Worms, H., and Canman, C. E. (2000). Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res 60:5934–5936.
Andegeko, Y., Moyal, L., Mitelman, L., Tsarfaty, I., Shiloh, Y., and Rotman, G. (2001). Nuclear retention of ATM at sites of DNA double strand breaks. J Biol Chem 276:38224–38230.
Anderson, C.W., and Appella, E. (2003). Signaling to the p53 tumor suppressor through pathways activated by genotoxic and non-genotoxic stresses. In R. A. Bradshaw and E. Dennis (eds), Handbook of Cell Signaling. Academic Press, New York, pp. 237–247.
Anderson, C.W., and Lees-Miller, S. P. (1992). The nuclear serine/threonine protein kinase DNA-PK. Crit Rev Eukaryot Gene Expr 2:283–314.
Anderson, M. E., 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.
Appella, E., and Anderson, C. W. (2001). Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem 268:2764–2772.
Ayed, A., Mulder, F. A. A., Yi, G.-S., Lu, Y., Kay, L. E., and Arrowsmith, C.H. (2001). Latent and active p53 are identical in conformation. Nat Struct Biol 8:756–760.
Bakkenist, C. J., and Kastan, M. B. (2003). DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421:499–506.
Banin, S., Moyal, L., Shieh, S.-Y., Taya, Y., Anderson, C.W., Chessa, L., Smorodinsky, N.I., Prives, C., Reiss, Y., Shiloh, Y., and Ziv, Y. (1998). Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281:1674–1677.
Bech-Otschir, D., Kraft, R., Huang, X., Henklein, P., Kapelari, B., Pollmann, C., and Dubiel, W. (2001). COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. EMBO J 20:1630–1639.
Bernstein, C., and Bernstein, H. (1991). Aging, Sex, and DNA Repair. Academic Press, San Diego, CA.
Bonner, W. M. (2003). Low-dose radiation: Thresholds, bystander effects, and adaptive responses. Proc Natl Acad Sci USA 100:4973–4975.
Bosotti, R., Isacchi, A., and Sonnhammer, E. L. L. (2000). FAT: a novel domain in PIK-related kinases. Trends Biochem Sci 25:225–227.
Brown, E. J., and Baltimore, D. (2003). Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev 17:615–628.
Bulavin, D.V., Amundson, S. A., and Fornace, Jr., A. J. (2002a). p38 and Chk1 kinases: different conductors for the G2/M checkpoint symphony. Curr Opin Genet Dev 12:92–97.
Bulavin, D. V., Demidov, O. N., Saito, S., Kauraniemi, P., Phillips, C., Amundson, S. A., Ambrosino, C., Sauter, G., Nebreda, A. R., Anderson, C. W., Kallioniemi, A., Fornace, Jr., A. J., and Appella, E. (2002b). Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. Nat Genet 31:210–215.
Bulavin, D. V., Saito, S., Hollander, M. C., Sakaguchi, K., Anderson, C. W., Appella, E., and Fornace Jr., A. J. (1999). Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. EMBO J 18:6845–6854.
Burma, S., Chen, B. P., Murphy, M., Kurimasa, A., and Chen, D. J. (2001). ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 276:42462–42467.
Canman, C. E. (2003). Checkpoint mediators: relaying signals from DNA strand breaks. Curr Biol 13:R488–R490.
Canman, C. E., Lim, D.-S., Cimprich, K. A., Taya, Y., Tamai, K., Sakaguchi, K., Appella, E., Kastan, M. B., and Siliciano, J. D. (1998). Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281:1677–1679.
Chao, C., Saito, S., Anderson, C. W., Appella, E., and Xu, Y. (2000). Phosphorylation of murine p53 at Ser-18 regulates the p53 responses to DNA damage. Proc Natl Acad Sci USA 97:11936–11941.
Chehab, N. H., Malikzay, A., Appel, M., and Halazonetis, T. D. (2000). Chk2/hCds1 functions as a DNA damage checkpoint in G1 by stabilizing p53. Genes Dev 14:278–288.
Chehab, N. H., Malikzay, A., Stavridi, E. S., and Halazonetis, T. D. (1999). Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc Natl Acad Sci USA 96:13777–13782.
Cho, Y., Gorina, S., Jeffrey, P. D., and Pavletich, N. P. (1994). Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 265:346–355.
Cline, S. D., and Hanawalt, P. C. (2003). Who’s on first in the cellular response to DNA damage? Nat Rev Mol Cell Biol 4:361–373.
Clore, G. M., Ernst, J., Clubb, R., Omichinski, J. G., Kennedy, W. M. P., Sakaguchi, K., Appella, E., and Gronenborn, A. M. (1995). Refined solution structure of the oligomerization domain of the tumour suppressor p53. Nat Struct Biol 2:321–333.
Cortez, D., Guntuku, S., Qin, J., and Elledge, S. J. (2001). ATR and ATRIP: partners in checkpoint signaling. Science 294:1713–1716.
Craig, A. L., Bray, S. E., Finlan, L. E., Kernohan, N. M., and Hupp, T. R. (2003). Signaling to p53: The use of phospho-specific antibodies to probe for in vivo kinase activation. Methods Mol Biol 234:171–202.
D’Amours, D., and Jackson, S. P. (2002). The Mre11 complex: at the crossroads of DNA repair and checkpoint signalling. Nat Rev Mol Cell Biol 3:317–327.
Denning, G., Jamieson, L., Maquat, L. E., Thompson, E. A., and Fields, A. P. (2001). Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein. J Biol Chem 276:22709–22714.
D’Orazi, G., Cecchinelli, B., Bruno, T., Manni, I., Higashimoto, Y., Saito, S., Gostissa, M., Coen, S., Marchetti, A., Del Sal, G., Piaggio, G., Fanciulli, M., Appella, E., and Soddu, S. (2002). Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis. Nat Cell Biol 4:11–19.
Dornan, D., and Hupp, T. R. (2001). Inhibition of p53-dependent transcription by BOX-I phospho-peptide mimetics that bind to p300. EMBO Rep 2:139–144.
Dumaz, N., and Meek, D. W. (1999). Serine 15 phosphorylation stimulates p53 transactivation but does not directly influence interaction with HDM2. EMBO J 18:7002–7010.
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.
Fei, P., and el-Deiry, W.S. (2003). P53 and radiation responses. Oncogene 22:5774–5783.
Fiscella, M., Zhang, H., Fan, S., Sakaguchi, K., Shen, S., Mercer, W. E., Vande Woude, G. F., O’Connor, P. M., and Appella, E. (1997). Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner. Proc Natl Acad Sci. USA 94:6048–6053.
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.
Hammond, E. M., Denko, N. C., Dorie, M. J., Abraham, R. T., and Giaccia, A. J. (2002). Hypoxia links ATR and p53 through replication arrest. Mol Cell Biol 22:1834–1843.
Hao, M., Lowy, A.M., Kapoor, M., Deffie, A., Liu, G., and Lozano, G. (1996). Mutation of phosphoserine 389 affects p53 function in vivo. J Biol Chem 271:29380–29385.
Higashimoto, Y., Saito, S., Tong, X.-H., Hong, A., Sakaguchi, K., Appella, E., and Anderson, C.W. (2000). Human p53 is phosphorylated on serines 6 and 9 in response to DNA damage-inducing agents. J Biol Chem 275:23199–23203.
Hofmann, T. G., Möller, A., Sirma, H., Zentgraf, H., Taya, Y., Dröge, 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.
Hofseth, L.J., Saito, S., Hussain, S.P., Espey, M.G., Miranda, K.M., Araki, Y., Jhappan, C., Higashimoto, Y., He, P., Linke, S.P., Quezado, M.M., Zurer, I., Rotter, V., Wink, D.A., Appella, E., and Harris, C.C. (2003). Nitric oxide-induced cellular stress and p53 activation in chronic inflammation. Proc Natl Acad Sci USA 100:143–148.
Hupp, T. R., and Lane, D. P. (1994). Regulation of the cryptic sequence-specific DNA-binding function of p53 by protein kinases. Cold Spring Harb Symp Quant Biol 59:195–206.
Hupp, T. R., Meek, D.W., Midgley, C. A., and Lane, D. P. (1992). Regulation of the specific DNA binding function of p53. Cell 71:875–886.
Itahana, K., Dimri, G., and Campisi, J. (2001). Regulation of cellular senescence by p53. Eur J Biochem 268:2784–2791.
Jallepalli, P. V., Leaguer, C., Vogelstein, B., and Benz, F. (2003). The Chk2 tumor suppressor is not required for p53 responses in human cancer cells. J Biol Chem 278:20475–20479.
Jeffrey, P. D., Gorina, S., and Pavletich, N. P. (1995). Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 angstroms. Science 267:1498–1502.
Jimenez, G. F., Bryntesson, F., Torres-Arzayus, M. I., Priestley, A., Beeche, M., Saito, S., Sakaguchi, K., Appella, E., Jeggo, P. A., Taccioli, G. E., Wahl, G. M., and Hubank, M. (1999). DNA-dependent protein kinase is not required for the p53-dependent response to DNA damage. Nature 400:81–83.
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.
Kaku, S., Iwahashi, Y., Kuraishi, A., Albor, A., Yamagishi, T., Nakaike, S., and Kulesz-Martin, M. (2001). Binding to the naturally occurring double p53 binding site of the Mdm2 promoter alleviates the requirement for p53 C-terminal activation. Nucleic Acids Res 29:1989–1993.
Kapoor, M., and Lozano, G. (1998). Functional activation of p53 via phosphorylation following DNA damage by UV but not γ radiation. Proc Natl Acad Sci USA 95:2834–2837.
Kim, E., and Deppert, W. (2003). The complex interactions of p53 with target DNA: we learn as we go. Biochem Cell Biol 81:141–150.
Kishi, H., Nakagawa, K., Matsumoto, M., Suga, M., Ando, M., Taya, Y., and Yamaizumi, M. (2001). Osmotic shock induces G1 arrest through p53 phosphorylation at Ser33 by activated p38MAPK without phosphorylation at Ser15 and Ser20. J Biol Chem 276:39115–39122.
Klein, C., Planker, E., Diercks, T., Kessler, H., Künkele, K.-P., 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.
Ko, L. J., and Prives, C. (1996). p53: puzzle and paradigm. Genes Dev 10:1054–1072.
Kozlov, S., Gueven, N., Keating, K., Ramsay, J., and Lavin, M. F. (2003). ATP activates ataxia-telangiectasia mutated (ATM) in vitro. Importance of autophosphorylation. J Biol Chem 278:9309–9317.
Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., and Pavletich, N. P. (1996). Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274:948–953.
Lambert, P. F., Kashanchi, F., Radonovich, M. F., Shiekhattar, R., and Brady, J. N. (1998). Phosphorylation of p53 serine 15 increases interaction with CBP. J Biol Chem 273:33048–33053.
Lees-Miller, S. P., Sakaguchi, K., Ullrich, S. J., Appella, E., and Anderson, C.W. (1992). Human DNA-activated protein kinase phosphorylates serines 15 and 37 in the amino-terminal transactivation domain of human p53. Mol Cell Biol 12:5041–5049.
Li, J., Yang, Y., Peng, Y., Austin, R. J., Van Eyndhoven, W. G., Nguyen, K. C. Q., Gabriele, T., McCurrach, M. E., Marks, J. R., Hoey, T., Lowe, S. W., and Powers, S. (2002). Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23. Nat Genet 31:133–134.
Lu, H., Taya, Y., Ikeda, M., and Levine, A. J. (1998). Ultraviolet radiation, but not radiation or etoposideinduced DNA damage, results in the phosphorylation of the murine p53 protein at serine-389. Proc Natl Acad Sci USA 95:6399–6402.
Mazur, S. J., Sakaguchi, K., Appella, E., Wang, X. W., Harris, C. C., and Bohr, V. A. (1999). Preferential binding of tumor suppressor p53 to positively or negatively supercoiled DNA involves the C-terminal domain. J Mol Biol 292:241–249.
Melchionna, R., Chen, X.-B., Blasina, A., and McGowan, C. H. (2000). Threonine 68 is required for radiation-induced phosphorylation and activation of Cds1. Nat Cell Biol 2:762–765.
Melchior, F., and Hengst, L. (2002). SUMO-1 and p53. Cell Cycle 1:245–249.
Mihara, M., Erster, S., Zaika, A., Petrenko, O., Chittenden, T., Pancoska, P., and Moll, U. M. (2003). p53 has a direct apoptogenic role at the mitochondria. Mol Cell 11:577–590.
Nakamura, S., Roth, J. A., and Mukhopadhyay, T. (2002). Multiple lysine mutations in the C-terminus of p53 make it resistant to degradation mediated by MDM2 but not by human papillomavirus E6 and induce growth inhibition in MDM2-overexpressing cells. Oncogene 21:2605–2610.
Nielsen, O. (2003). COP9 signalosome: a provider of DNA building blocks. Curr Biol 13:R565–R567.
Oda, K., Arakawa, H., Tanaka, T., Matsuda, K., Tanikawa, C., Mori, T., Nishimori, H., Tamai, K., Tokino, T., Nakamura, Y., and Taya, Y. (2000). p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell 102:849–862.
Oren, M. (2003). Decision making by p53: life, death and cancer. Cell Death Differ 10:431–442.
Palecek, E., Vlk, D., Stanková, V., Brázda, V., Vojtesek, B., Hupp, T. R., Schaper, A., and Jovin, T. M. (1997). Tumor suppressor protein p53 binds preferentially to supercoiled DNA. Oncogene 15:2201–2209.
Paull, T. T., Rogakou, E. P., Yamazaki, V., Kirchgessner, C. U., Gellert, M., and Bonner, W. M. (2000). A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol 10:886–895.
Petrini, J. H. J., and Stracker, T. H. (2003). The cellular response to DNA double-strand breaks: defining the sensors and mediators. Trends Cell Biol 13:458–462.
Prives, C., and Manley, J. L. (2001). Why is p53 acetylated? Cell 107:815–818.
Redon, C., Pilch, D., Rogakou, E., Sedelnikova, O., Newrock, K., and Bonner, W. (2002). Histone H2A variants H2AX and H2AZ. Curr Opin Genet Dev 12:162–169.
Rippin, T. M., Freund, S. M. V., Veprintsev, D. B., and Fersht, A. R. (2002). Recognition of DNA by p53 core domain and location of intermolecular contacts of cooperative binding. J Mol Biol 319:351–358.
Saito, S., Goodarzi, A. A., Higashimoto, Y., Noda, Y., Lees-Miller, S. P., Appella, E., and Anderson, C. W. (2002). ATM mediates phosphorylation at multiple p53 sites, including Ser46, in response to ionizing radiation. J Biol Chem 277:12491–12494.
Saito, S., Yamaguchi, H., Higashimoto, Y., Chao, C., Xu, Y., Fornace, Jr., A. J., Appella, E., and Anderson, C. W. (2003). Phosphorylation site interdependence of human p53 post-translational modifications in response to stress. J Biol Chem 278:37536–37544.
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.
Sakaguchi, K., Sakamoto, H., Lewis, M. S., Anderson, C. W., Erickson, J. W., Appella, E., and Xie, D. (1997). Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53. Biochemistry 36:10117–10124.
Sax, J. K., and el-Deiry, W. S. (2003). p53 downstream targets and chemosensitivity. Cell Death Differ 10:413–417.
Schon, O., Friedler, A., Bycroft, M., Freund, S. M. V., and Fersht, A. (2002). Molecular mechanism of the interaction between MDM2 and p53. J Mol Biol 323:491–501.
Schultz, L. B., Chehab, N. H., Malikzay, A., and Halazonetis, T. D. (2000). p53 binding protein 1 (53BP1) is an early participant in the cellular response to DNA double-strand breaks. J Cell Biol 151:1381–1390.
Shieh, S.-Y., Ahn, J., Tamai, K., Taya, Y., and Prives, C. (2000). The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev 14:289–300.
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.
Shiloh, Y. (2003). ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 3:155–168.
Siliciano, J. D., Canman, C. E., Taya, Y., Sakaguchi, K., Appella, E., and Kastan, M. B. (1997). DNA damage induces phosphorylation of the amino terminus of p53. Genes Dev 11:3471–3481.
Smith, G. C. M., Cary, R. B., Lakin, N. D., Hann, B. C., Teo, S.-H., Chen, D. J., and Jackson S. P. (1999). Purification and DNA binding properties of the ataxia-telangiectasia gene product ATM. Proc Natl Acad Sci USA 96:11134–11139.
Smith, M. L., and Seo, Y. R. (2002). p53 regulation of DNA excision repair pathways. Mutagenesis 17:149–156.
Sutherland, B. M., Bennett, P. V., Sidorkina, O., and Laval, J. (2000). Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation. Proc Natl Acad Sci USA 97:103–108.
Suzuki, K., Kodama, S., and Watanabe, M. (1999). Recruitment of ATM protein to double strand DNA irradiated with ionizing radiation. J Biol Chem 274:25571–25575.
Takai, H., Naka, K., Okada, Y., Watanabe, M., Harada, N., Saito, S., Anderson, C.W., Appella, E., Nakanishi, M., Suzuki, H., Nagashima, K., Sawa, H., Ikeda, K., and Motoyama, N. (2002). Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription. EMBO J 21:5195–5205.
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.
Tibbetts, R. S., Brumbaugh, K. M., Williams, J. M., Sarkaria, J. N., Cliby, W. A., Shieh, S.-Y., Taya, Y., Prives, C., and Abraham, R. T. (1999). A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev 13:152–157.
Tibbetts, R. S., Cortez, D., Brumbaugh, K. M., Scully, R., Livingston, D., Elledge, S. J., and Abraham, R. T. (2000). Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. Genes Dev 14:2989–3002.
Uziel, T., Lerenthal, Y., Moyal, L., Andegeko, Y., Mittelman, L., and Shiloh, Y. (2003). Requirement of the MRN complex for ATM activation by DNA damage. EMBO J 22:5612–5621.
Vousden, K. H., and Lu, X. (2002). Live or let die: the cell’s response to p53. Nat Rev Cancer 2:594–604.
Wahl, G.M., and Carr, A.M. (2001). The evolution of diverse biological responses to DNA damage: insights from yeast and p53. Nat Cell Biol 3:E277–E286.
Wang, Y., and Prives, C. (1995). Increased and altered DNA binding of human p53 by S and G2/M but not G1 cyclin-dependent kinases. Nature 376:88–91.
Wang, Y.-H., Tsay, Y.-G., Tan, B.C.-M., Lo, W.-Y., and Lee, S.-C. (2003). Identification and characterization of a novel p300-mediated p53 acetylation site, lysine 305. J Biol Chem 278:25568–25576.
Waterman, M. J. F., Stavridi, E. S., Waterman, J. L. F., and Halazonetis, T. D. (1998). ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins. Nat Genet 19:175–178.
Wu, Z., Earle, J., Saito, S., Anderson, C. W., Appella, E., and Xu, Y. (2002). Mutation of mouse p53 Ser23 and the response to DNA damage. Mol Cell Biol 22:2441–2449.
Yamashita, A., Ohnishi, T., Kashima, I., Taya, Y., and Ohno, S. (2001). Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay. Genes Dev 15:2215–2228.
Yarosh, D. B., Cruz, Jr., P. D., Dougherty, I., Bizios, N., Kibitel, J., Goodtzova, K., Both, D., Goldfarb, S., Green, B., and Brown, D. (2000). FRAP DNA-dependent protein kinase mediates a late signal transduced from ultraviolet-induced DNA damage. J Invest Dermatol 114:1005–1010.
Zhang, Y., and Xiong, Y. (2001). A p53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation. Science 292:1910–1915.
Zhao, H., and Piwnica-Worms, H. (2001). ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol Cell Biol 21:4129–4139.
Zilfou, J. T., Hoffman, W. H., Sank, M., George, D. L., 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.
Zou, L., Cortez, D., and Elledge, S. J. (2002). Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin. Genes Dev 16:198–208.
Zou, L., and Elledge, S. J. (2003). Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300:1542–1548.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer Science Business Media, Inc.
About this chapter
Cite this chapter
Anderson, C.W., Appella, E. (2005). Posttranslational Modifications of p53: Upstream Signaling Pathways. 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_5
Download citation
DOI: https://doi.org/10.1007/0-387-30127-5_5
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-24135-7
Online ISBN: 978-0-387-30127-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)