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Regulation of cellular functions of p53 by ubiquitination  

Jung, Jin-Hyuk (Functional Genoproteome Research Centre, Konkuk University)
Lee, Joon-Young (Functional Genoproteome Research Centre, Konkuk University)
Lee, Sun-Mi (Functional Genoproteome Research Centre, Konkuk University)
Choe, Tae-Boo (Department of Microbial Engineering, Konkuk University)
An, Sung-Kwan (Functional Genoproteome Research Centre, Konkuk University)
Publication Information
KSBB Journal / v.24, no.3, 2009 , pp. 217-226 More about this Journal
Abstract
p53 undergoes various post-translational modifications, including phosphorylation, ubiquitination, sumoylation, acetylation, methylation, and poly(ADP-ribosyl)ation. Modification of p53 widely affects to various functions of p53. Acetylation and phosphorylation of p53 have been studied for regulating its transcriptional activity which is observed in various stress condition. Otherwise, ubiquitination of p53 by Mdm2 has been well-studied as a canonical ubiquitin-mediated proteasomal degradation pathway. Moreover several investigators have recently reported that ubiquitination of p53 modulates not only its proteasome-dependent degradation by poly-ubiquitination but also its localization and transcriptional activity by mono-ubiquitination which usually does not serve the proteasome dependent degradation. Here we review recent studies on the cellular functions of p53 regulated by post-translational modifications, particularly focusing on mechanisms of ubiquitination.
Keywords
p53; ubiquitin-mediated degradation; localization; modulation of transcriptional activity;
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1 Baker, S. J., A. C. Preisinger, J. M. Jessup, C. Paraskeva, S. Mrakowitz, J. K. Willson, S. Hamilton, and B. Voge1stein (1990), p53 gene mutation occur in combination with 17p allelic deletions as late events in cololectal tumorigenesis, Cancer Res. 23, 717-722
2 Hsu, I. C., R. A. Metcalf, T. Sun, J. A. Welsh, N. J. Wang, and C. C. Harris (1991), Mutational hotspot in the p53 gene in human hepatocellular carcinomas, Nature 350, 427-428   DOI   ScienceOn
3 el-Deiry, W. S., J. W. Harper， P. M. O 'Connor, V. E. Velculescu, C. E. canman, J. Jackman, J. A. Pietenpol, M. Burrell, D. E. Hill, and Y. Wang (1994), WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis, Cancer Res. 54, 1169-1174   PUBMED
4 Terrell, J., S. Shih, R. Dunn, and L. Hicke (1998), A fuction for monoubiquitination in the intemalization of a G protein-coupled receptor, Mol. Cell 1, 193-202   DOI   ScienceOn
5 Scheffner, M., B. A. Wemess, J. M. Huibregtse, A. J. Levine, and P. M. Howley (1990), The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53, Cell 63, 1129-1136   DOI   ScienceOn
6 Courjal, F., M. Cuny, C. Rodriguez, G. Louason, P. Speiser, D. Katsaros, M. M. Tanner, R. Zeillinger, and C. Theillet (1996), DNA amplifications at 20q13 and MDM2 define distinct subsets of evolved breast and ovarian tumours, Br. J. Cancer 74, 1984-1989   DOI   PUBMED   ScienceOn
7 Zhang, Y., Y. Xiong, and W. G. Yarbrough (1998), ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways, Cell 92, 725-734   DOI   ScienceOn
8 Li, M., D. Chen, A. Shiloh, J. Luo, A. Y. Nikolaev, J. Qin, and W. Gu (2002), Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization, Nature 416, 648-653   DOI   ScienceOn
9 Shieh, S. Y., M. Ikeda, Y. Taya, and C. Prives (1997), DNA damage-induced phosphory lation of p53 alleviates inhibition by MDM2, Cell 91, 325-334   DOI   ScienceOn
10 Honda, R. and H. Yasuda (1999), Association of p19 (ARF) with Mdm2 inhibits ubiquitin ligase acivity of Mdm2 for tumor suppressor p53, EMBO J. 18, 22-27   DOI   ScienceOn
11 Colaluca, I. N., D. Tosoni, P. Nuciforo, F. Senic-Matuglia, V. Galimberti, G. Viale, S‘ Pece, and P. P. di Fiore (2008), NUMB controls p53 tumour suppressor activity, Nature 451, 76-80   DOI   ScienceOn
12 Osterlund, M. T., L. H. Ang, and X. W. Deng (1999), The role of COP1 in repression of Arabidopsis photomorphogenic development, Trends Cell Biol. 9, 113-118   DOI   ScienceOn
13 Kojima, K., M. Konopleva, T. McQueen, S. O ’Brien, W. Plunkett and M. Andreeff (2006), Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcriptíondependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to tludarabine in chronic lymphocytic leukemia, Blood 108, 993-1000   DOI   ScienceOn
14 Bond, G. L., K. M. Hirshfield, T. Kirchhoff, G. Alexe, E. E. Bond, H. Robins, F. Bartel, H. Taubert, P. Wuerl, W. Hait, D. Toppmeyer, K. Offit, and A. J. Levine (2006), MDM2 SNP 309 accelerates tumor forrnation in a gender-specific and horrnone-dependent manner, Cancer Res. 66, 5104-5110   DOI   ScienceOn
15 Hu, W., Z. Feng, L. Ma, J. Wagner, J. J. Rice, G. Stolovitzky, and A. J. Levine (2007), A Single nucleotide polymorphism in the MDM2 gene disrupts the oscillation of p53 and MDM2 levels in cells, Cancer Res. 67, 2757-2865   DOI   ScienceOn
16 Kato, S., J. Ding, E. Pisck, U. S. Jhala, and K. Du (2008), COP1 Functions as a FoxO1 Ubiquitin E3 Ligase to Regulate FoxO1-mediated Gene Expression, J. Biol. Chem. 283, 35464-35473   DOI   ScienceOn
17 Hattori, T.,T. Isobe, K. Abe, H. Kikuchi, K. Kitagawa, T. Oda, C. Uchida, and M. Kitagawa (2007), Pirh2 promotes ubiquitin-dependent degradation of the cyclindependent kinase inhibitor p27Kip1, Cancer Res. 67, 10789-10795   DOI   ScienceOn
18 Freedman, D. A. and A. J. Levine (1998), Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6, Mol. Cell Biol. 18, 7288-7293   PUBMED   ScienceOn
19 Yang, W., L. M. Rozan, E. R. McDonald 3rd, A. Navaraj, J. J. Liu, E. M. Matthew, W. Wang, D. T. Dicker and W. S. EI-Deiry (2007), CARPs are ubiquitin ligases that promote MDM2-independent p53 and phospho-p53ser20 degradation. J. Biol. Chem. 282, 3273-3281   DOI   ScienceOn
20 Chen, D., N. Kon, M. Li, W. Zhang, J. Qin, and W. Gu (2005), ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor, Cell 121, 1071-1083   DOI   ScienceOn
21 Boutell, C. and R. D. Everett (2003), The herpes simplex virus type 1 (HSV-1) regulatory protein ICP0 interacts with and ubiquitinates p53, J. Biol. Chem. 278, 36596-36602   DOI   ScienceOn
22 Barak, Y., T. Juven, R. Haffuer, and M. Oren (1993), Mdm2 expression is induced by wild type p53 activity, EMBO J. 12, 461-468   PUBMED   ScienceOn
23 Khosravi, R., R. Maya, T. Cottlieb, M. Oren, Y. Shiloh, and D. Shkedy (1999), Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage, Proc. Natl. Acad. Sci. USA 96, 14973-14977   DOI   ScienceOn
24 Dias, S. S., D. M. Milne, and D. W. Meek (2006), c-Abl phosphorylates Hdm2 at tyrosine 276 in response to DNA damage and regulates interaction with ARF, Oncogene 25, 6666-6671   DOI   ScienceOn
25 I. R. Logan, L. Gaughan, S. R McCracken, V. Sapountzi, H. Y. Leung, and C. N. Robson (2006), Human PIRH2 enhances androgen receptor signaling through inhibition of histone deacetylase 1 and is overexpressed in prostate cancer, Mol. Cell Biol. 26, 6502-6510   DOI   ScienceOn
26 Le Cam, L., L. K. Linares, C. Paul, E. Julien, M. Lacroix, E. Hatchi, R. Triboulet, G. Bossis, A. Shmueli, M. S. Rodriguez, O. Coux, and C. Sardet (2006), E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation, Cell 127, 775-788   DOI   ScienceOn
27 Stommel, J. M., N. D. Marchenko, G. S. Jimenez, U. M. Moll, T. J. Hope, and G. M. Wahl (1999), A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking, EMBO J. 18, 1660-1672   DOI   ScienceOn
28 Li, M., D. Chen, A. Shiloh, J. Luo, A. Y. Nikolaev, J. Qin, and W. Gu (2002), Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization, Nature 416, 648-653   DOI   ScienceOn
29 Tanaka, T., S. Ohkubo, I. Tatsuno, and C. Prives (2007), hCAS/CSEIL associates with chromatin and regulates expression of select p53 target genes, Cell 130, 638-650   DOI   ScienceOn
30 Tang, Y., W. Zhao, Y. Chen, Y. Zhao, and W. Gu (2008), Acetylation is indispensable for p53 activation, Cell 133, 612-626   DOI   ScienceOn
31 Yonish-Rouach, E., D. Resnitzky, J. Lotem, L. Sachs, A. Kimchi, and M. Oren (1991), Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6, Nature 352, 345-347   DOI   ScienceOn
32 Sidransky, D., A. von Eschenbach, Y. C. Tsai, P. Jones, I. Summerhayes, F. Marshall, M. Paul, P. Green, S. R. Hamilton, and P. Frost (1991), Identification of p53 gene mutations in bladder cancers and urine samples, Science 252, 706-709   DOI   PUBMED
33 Sheng, Y., R. C. Laister, A. Lemak, B. Wu, E. Tai, S. Duan, J. Lukin, M. Sunnerhagen, S. Srisailam, M. Karra, S. Benchimol, and C. Arrowsrnith (2008), Molecular basis of Pirh2-mediated p53 ubiquitylation, Nat. Struct. Mol. Biol. 15, 1334-1342   DOI   ScienceOn
34 Marchenko, N. D., S. Wolff, S. Erster, K. Becker, and U. M. Moll (2007), Monoubiquitylation promotes rnitochondrial p53 translocation, EMBO J. 26, 923-934   DOI   ScienceOn
35 Shaulsky, G., A. Ben-Ze'ev, and V. Rotter (1990), Subcellular distribution of the p53 protein during the cell cycle of Balb/c 3T3 cells, Olcogene 5, 1707-1711
36 Middler, G., K. Zerf, S. Jenovai, A. Thulig, M. Tschodrich-Rotter, U. Kubitscheck, and R. Peters (1997), The tumor suppressor p53 is subject to both nuclear import and export, and both are fast, energy-deendent and lectin-inhibited, Oncogene 14, 1407-1417   DOI   ScienceOn
37 Mayr, G. A., M. Reed, P. Wang, Y. Wang, J. F. Schweds, and P. Tegtmeyer (1995), Serine phosphorylation in the NH2 terrninus of p53 facilitates transactivation, Cancer Res. 55, 2410-2417   PUBMED   ScienceOn
38 Chan, W. M., M. C. Mak, T. K. Fung, A. Lau, W. Y. Siu, and R. Y. Poon (2006), Uboquitnation of p53 at multiple sites in the DNA-binding domain, Mol. Cancer Res. 4, 15-25   DOI   ScienceOn
39 Wu, X., J. H. Bayle, D. Olson, and A. J. Levine (1993), The p53-mdm-2 autoregulatory feedback loop, Genes Dev. 7, 1126-1132   DOI   ScienceOn
40 Jr Haluska, P., A. Saleem, Z. Rasheed, F. Ahrned, E. W. Su, L. F. Liu, and E. H. Rubin (1999), Interaction between human topoisomerase I and a novel RING finger/ arginine-serine protein, Nucleic Acids Res. 27, 2538-2544   DOI   ScienceOn
41 Kastan, M. B., Q. Zhan, W. S. e1-Deiry, F. Carrier, T. Jacks, W. V. Walsh, B. S. Plunkett, B. Vogelstein, and A. J. Fomace Jr (1992), A mammalian cell cycle checkpoint pathway uti1izing p53 and GADD45 is defective in ataxia-telangiectasia, Cell 71, 587-597   DOI   ScienceOn
42 Montes, de Oca Luna R., D. S. Wagner, and G. Lozano (1995), Rescue of early embryonic lethalíty in mdm2-deficient mice by deletion of p53, Nature 378, 203-206   DOI   ScienceOn
43 Hou, Y., A. G. von Amim, and X. W. Deng (1993), A new class of Arabidopsis constitutive photomorphogenic genes involved in regulating cotyledon development, Plant Cell 5, 329-339   DOI   ScienceOn
44 Oh, W., E. W. Lee, Y. H. Sung, M. R. Yang, J. Ghim, H. W. Lee, and J. Song (2006), Jabl induces the cytoplasmic localization and degradation of p53 in coordination with Hdm2, J. Biol. chem. 281, 17457-17465   DOI   ScienceOn
45 Hochstrasser, M. (1996), Ubiquitin-depcndent protein degradation, Annu. Rev. Genet. 30, 405-439   DOI   PUBMED   ScienceOn
46 Rajendra, R., D. Malegaonkar, P. Pungaliya, H. Marshall, Z. Rasheed, J. Brownell, L. F. Liu, S. Lutzker, A. Saleem, and E. H. Rubin (2004), Topors functions as and E3 ubiquitin ligase with specific E2 enzymes and ubiquitianates p 53, J. Biol. Chem. 279, 36440-36444   DOI   ScienceOn
47 Boddy, M. N., P. S. Freemont, and K. L. Borden (1994), The p53-associated protein MDM2 contains a newly characterized zinc-binding domain called the RING finger, Trends Biochem. Sci. 19, 198-199   DOI   PUBMED   ScienceOn
48 Liao W, Q. Xiao, V. Tchikov, K. Fujita, W. Yang, S. Wincovitch, S. Garfield, D. Conze, W. S. EI-Deiry, S. Schutez, and S. M. Srinivasula (2008), CARP-2 is an endosome-associated ubiquitin ligase for RIP and regulates TNF-induced NF-kappaB activation, Curr. Biol. 18, 641-649   DOI   PUBMED   ScienceOn
49 Gu, W. and R. G. Roeder (1997), Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90, 595-606   DOI   ScienceOn
50 Owen-Schaub, L. B., W. Zhang, J. C. Cusack, L. S. Angelo, S. M. Santee, T. Fujiwara, J. A. Roth, A. B. Deisseroth, W. W. Zhang, and E. Kruzel (1995), Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression, Mol. Cell Biol. 15, 3032-3040   DOI   PUBMED
51 Guan, B., P. Pungaliya, X. Li, C. Uquillas, L. N. Mutton, E. H. Rubin, and C. J. Bieberich (2008), Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1, J. Biol. Chem. 283, 4834-4840   DOI   ScienceOn
52 Zhong, Q., W. Gao, F. Du, and X. Wang (2005), Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis, Cell 121, 1085-1095   DOI   ScienceOn
53 Yamasaki, S., N. Yagishita, T. Sasaki, M. Nakazawa, Y. Kato, T. Yamadera, E. Bae, S. Toriyarna, R. Ikeda, L. Zhang, K. Fujitani, E. Yoo, K. Tsuchimochi, T. Ohta, N. Araya, H. Fujita, S. Aratani, K. Eguchi, S. Komiya, I. Maruyama, N. Higashi, M. Sato, H. Senoo, T. Ochi, S. Yokoyama, T. Amano, J. Kim, S. Gay, A. Fukamizu, K. Nishioka, K. Tanaka, and T. Nakajima (2007), Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquuitin ligase Synoviolin, EMBO J. 26, 113-122   DOI   ScienceOn
54 Foo, R. S., L. K. Chan, R. N. Kitsis, and M. R. Bennett (2007), Ubiquitination and degradation of the anti-apoptotic protein ARC by MDM2, J. Biol. Chem. 282, 5529-5535   DOI   ScienceOn
55 Paulin, F. E., M. O’Neill, G. McGregor, A. Cassidy, A. Ashfield, C. W. Ali, A. J. Munro, L. Baker, C. A. Purdie, D. P. Lane, and A. M. Thompson (2008), MDM2 SNP309 is associated with high grade node positive breast tumours and is in linkage disequilibrium with a novel MDM2 intron 1 polymorphism, BMC Cancer. 8, 281   DOI   PUBMED   ScienceOn
56 Murray, A. (1995), Cyclin ubiquitination: the destructive end of mitosis, Cell 81, 149-152   DOI   PUBMED   ScienceOn
57 Siliciano, J. D., C. E. Canman, Y. Taya, K. Sakaguchi, E. Appella, and M. B. Kastan (1997), DNA damage induces phosphorylation of the amino tenninus of p53, Genes Dev. 11, 3471-3481   DOI   ScienceOn
58 Nakano, K. and K. H. Vousden (2001), PUMA, a novel proapoptotic gene, is induced by p53, Mol. Cell 7, 683-694   DOI   ScienceOn
59 Vassilev, L. T., B. T. Vu, B. Graves, D. Carvajal, F. Podlaski, Z. Filipovic, N. Kong, U. Kammlott, C. Lukacs, C. Klein, N. Fotouhi and E. A. Liu (2004), In vivo activation of the p53 pathway by smallmolecule antagonists of MDM2, Science 303, 844-848   DOI   PUBMED   ScienceOn
60 Lane, D. P. (1992), Cancer. p53, guardian of the genome, Nature 358, 15-16   DOI   PUBMED   ScienceOn
61 Kruse, J. P. and W. Gu (2008), MSL2 promotes MDM2 independent cytoplasrnic localization of p53, Epub ahead of print 2008 Nov 25
62 Hollstein, M., D. Sidransky, B. Vogelstein, and C. C. Harris (1991), p53 mutations in human cancers, Science 253, 49-53   DOI   PUBMED
63 Brooks, C. L. and W. Gu (2006), p53 ubiquitination: Mdm2 and beyond, Mol. Cell 21, 307-315   DOI   ScienceOn
64 Grossman, S. R., M. E. Deato, C. Brignone H.M. Chan, A. L. Kung, H. Tagami, Y. Nakatani, and D. M. Livingston (2003), Polyubiquitination of p53 by a ubiquitin ligase activity of p300, Science 300, 342-344   DOI   PUBMED   ScienceOn
65 Nikolaev, A. Y., M. Li, N. Puskas, J. Qin, and W. Gu (2003), Parc: a cytoplasmic anchor for p53, Cell 112, 29-40   DOI   ScienceOn
66 Ofir-Rosenfeld, Y., K. Boggs, D. Michael, M. B. Kastan, and M. Oren, (2008), Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26, Mol. Cell 32, 180-189   DOI   ScienceOn
67 Mullen, M. A., D. M. Ciufo, and G. S. Hayward (1994), Mapping of intracellular localization domains and evidence for colocalization interactions between the IE 110 and IE175 nuclear transactivator proteins of herpes simplex virus, J. Virol. 68, 3250-3266   PUBMED   ScienceOn
68 Vaziri, H., M. D. West, R. C. Allsopp, T. S. Davison, Y. S. Wu, C. H. Arrowsmith, G. G. Poirier, and S. Benchimol (1997), ATM-dependent telomere loss in aging human diploid fibrob1asts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase, EMBO J. 16, 6018-6033   DOI   ScienceOn
69 Joseph, T. W., A. Zaika, and U. M. Moll (2003), Nuclear and cytoplasmic degradation of endogenous p53 and HDM2 occurs during down-regulation of the p53 response after multiple types of DNA damage, FASEB J. 17, 1622-1630   DOI   ScienceOn
70 Li, M., C. L. Brooks F. Wu-Baer, D. Chen, R. Baer, and W. Gu (2003), Mono-versus polyubiquitination: differential control of p53 fate by Mdm2, Science 302, 1972-1975   DOI   PUBMED   ScienceOn
71 Stacey, M. G., S. N. Hicks, and A. G. von Amim (1999), Discrete domains mediate the light-responsive nuclear and cytoplasmic localization of Arabidopsis COP1, Plant Cell 11, 349-364   DOI   ScienceOn
72 Itahana, K., H. Mao, A. Jin, Y. Itahana, H. V. Clegg, K. P. Bhat, V. L. Godfrey, G. I. Evan, and Y. Zhang (2007), Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase actívity in the mouse reveals mechanistíc insights into p53 regulation, Cancer Cell 12, 355-366   DOI   ScienceOn
73 Moriuchi, H., M. Moriuchi, and J. I. Cohen (1994), The RING finger domain of the varicella-zoster virus open reading frame 61 protein is required for its transregulatory functions, Virol. 205, 238-246   DOI   ScienceOn
74 Giannakakou, P., D. L. Sackett, Y. Ward, K. R. Webster, M. V. Blagosklonny, and T. Fojo (2000), p53 is associated with cellular microtubules and is transported to the nucleus by dynein, Nat. Cell Biol. 2, 709-719   DOI   ScienceOn
75 Lohrum, M. A., D. B. Woods, R. L. Ludwig, E. Balint, and K. H. Vousden (2001), C-terminal ubiquitination of p53 contributes to nuclear export, Mol. Cell Biol. 21, 8521-8532   DOI   ScienceOn
76 Liu, L., D. M. Scolnick, R. C. Trievel, H. B. Zhang, R. Marmorstein, T. D. Halazonetis, and S. L. Berger (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   ScienceOn
77 Miyashita, T. and J. C. Reed (1995), Tumor suppressor p53 is a direct transcriptional activator of the human bax gene, Cell 80, 293-299   DOI   ScienceOn
78 Weake, V. M. and J. L. Workman (2008), Histone ubiquitination: triggering gene activity, Mol. Cell 29, 653-663   DOI   ScienceOn
79 Jones, S. N., A. E. Roe, L. A. Donehower, and A. Bradley (1995), Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53, Nature 378, 206-208   DOI   ScienceOn
80 Von Amim, A. G. and X. W. Deng (1993), Ring finger motif of Arabidopsis thaliana COP1 defmes a new class of zinc-binding domain, J. Biol. Chem. 268, 19626-19631   PUBMED   ScienceOn
81 Sykes, S. M., H. S. Mellert, M. A. Holbert, K. Li, R. Marmorstein, W. S. Lane, and S. B. McMahon (2006), Acetylation of the p53 DNA-binding domain regulates apoptosis induction, Mol. Cell 24, 841-851   DOI   ScienceOn
82 Das, S., L. Raj, B. Zhao, Y. Kimura, A. Bemstein, S. A. Aaronson, and S. W. Lee (2007), Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation, Cell 130, 624-637   DOI   ScienceOn
83 Bond, J., M. Haughton, J. Blaydes, V. Gire, D. Wynford-Thomas, and F. Wyllie (1996), Evidence that transcriptional activation by p53 plays a direct role in the induction of cellular senescence, Oncogene 13, 2097-2104   PUBMED
84 Mihara, M., S. Erster, A. Zaika, O. Petrenko, T. Chittenden, P. Pancoska, and U. M. Moll (2003), p53 has a direct apoptogenic role at the mitochondria, Mol. Cell 11, 577-590   DOI   ScienceOn
85 Mayo, L. D. and D. B. Donner (2001), A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus, Proc. Natl. Acad. Sci. USA 98, 11598-11603   DOI   ScienceOn
86 Crighton, D., S. Wilkinson, J. O ’Prey, N. Syed, P. Smith, P. R. Harrison, M. Gasco, O. Garrone, T. Crook, and K. M. Ryan (2006), DRAM, a p53-induced modulator of autophagy, is critical for apoptosis, Cell 126, 121-134   DOI   ScienceOn
87 Doman, D., H. Shimizu, A. Mah, T. Dudhela, M. Eby, KO’rourke, S. Seshagiri， and V. M. Dixit (2006), ATM engages autodegradation of the E3 ubiquitin ligase COP1 after DNA damage, Science 313, 1122-1126   DOI   PUBMED   ScienceOn
88 Buschmann, T., S. Y. Fuchs, C. G. Lee, Z. Q. Pan, and Z. Ronai (2000), SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53, Cell 101, 753-762   DOI   ScienceOn
89 Geyer, R. K., Z. K. Yu, and C. G. Maki (2000), The MDM2 RING-finger domain is required to promote p53 nuclear export, Nat. Cell Biol. 2, 569-573   DOI   ScienceOn
90 Thrower, J. S., L. Hoffman, M. Rechsteiner, and C. M. Pickart (2000), Recognition of the polyubiquitin proteolytic signal, EMBO J. 19, 94-102   DOI   ScienceOn
91 Dulic, V., W. K. Kau:frnann, S. J. Wilson, T. D. Tlsty, E. Lees, J. W. Harper, S. J. Elledge, and S. I. Reed (1994), p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiationinduced G1 arrest, Cell 76, 1013-1023   DOI   ScienceOn
92 Duan, S., Z. Yao, D. Hou, Z. Wu, W. G. Zhu and M. Wu (2007), Phosphorylation of Pirh2 by calmodulindependent kinase II impairs its ability to ubiquitinate p53, EMBO J. 26, 3062-3074   DOI   ScienceOn
93 Oda, E., R. Ohki, H. Murasawa, J. Nemoto, T. Shibue, T. Yamashita, T. Tokino, T. Taniguchi, and N. Tanaka (2000), Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis, Science 288, 1053-1058   DOI   PUBMED   ScienceOn
94 Roth, J., M. Dobbelstein, D. A. Freedman, T. Shenk, and A. J. Levine (1998), Nucleo-cytoplasrnic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein, EMBO J. 17, 554-564   DOI   ScienceOn
95 Laine, A., I. Topisirovic, D. Zhai, J. C. Reed, K. L. Borden, and Z. Ronai (2006), Regulation of p53 localization and activity by Ubc13, Mol. Cell Biol. 26, 8901-8913   DOI   ScienceOn
96 Andrews, P., Y. J. He, and Y. Xiong (2006), Cytoplasmic localized ubiquitin ligase cullin 7 binds to p53 and promotes cell growth by antagonizing p53 function, Oncogene 25, 4534-4548   DOI   ScienceOn
97 Grossman, S. R., M. Perez, A. L. Kung, M. Joseph, C. Mansur, Z. X. Xiao, S. Kumar, P. M. Howley, and D. M. Livingston (1998), p300/MDM2 complexes participate in MDM2-mediated p53 degradation, Mol. Cell 2, 405-415   DOI   ScienceOn
98 Shaulsky, G., N. Goldfinger, A. Ben-Ze' ev, and V. Rotter (1990), Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis, Mol. Cell Biol. 10, 6565-6577   DOI   PUBMED   ScienceOn
99 Barlev, N. A., L. Liu, N. H. Chehab, K. Mansfield, K. G. Harris, T. D. Halazonetis, and S. L. Berger (2001), Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases, Mol. Cell 8, 1243-1254   DOI   ScienceOn
100 Lain, S., J. J. Hollick, J. Campbell, O. D. Staples, M. Higgins, M. Aoubala, A. McCarthy, V. Appleyard, K. E. Murray, L. Baker, A. Thompson, J. Mathers, S. J. Holland, M. J. Stark, G. Pass, J. Woods, D. P. Lane, and N. J. Westwood (2008), Discovery, in vivo activity, and mechanism of action of a smallmolecule p53 activator, Cancer Cell 13, 454-463   DOI   ScienceOn
101 Chau, V., J. W. Tobias, A. Bachmair, D. Marriott, D. J. Ecker, D. K. Gonda and A. Varshavsky (1989), A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein, Science 243, 1576-1583   DOI   PUBMED
102 Fakharzadeh, S. S., S. P. Trusko, and D. L. George (1991), Tumorigenic potential associated with enhanced expression of a gene that ís amplified in a mouse tumor cell line, EMBO J. 10, 1565-1569   PUBMED
103 Pan, Y. and J. Chen (2003), MDM2 promotes ubiquitination and degradation of MDMX, Mol. Cell Biol. 23, 5113-5121   DOI   ScienceOn
104 Ogryzko, V. V., R. L. Schiltz, V. Russanova, B. H. Howard, and Y. Nakatan (1996), The transcriptional coactivators p300 and CBP are histone acetyltransferases, Cell 87, 953-959   DOI   ScienceOn
105 Lowe, S. W., E. M. Schmitt, S. W. Smith, B. A. Osbome, and T. Jacks (1993), p53 is required for radiation-induced apoptosis in mouse thymocytes, Nature 362, 847-849   DOI   ScienceOn
106 Hershko, A. and A. Ciechanover (1992), The ubiquitin system for protein degradation, Annu. Rev. Biochem. 61, 761-807   DOI   ScienceOn
107 Doman, D., I. Wertz, H. Shimizu, D. Amott, G. D. Frantz, P. Dowd, K. O ’Rourke, H. Koeppen and V. M. Dixit (2004), The ubiquitin ligase COPI is a critical negative regulator of p53, Nature 429, 86-92   DOI   ScienceOn
108 Logan, I. R., V. Sapountzi, L. Gaughan, D. E. Neal, and C. N. Robson (2004), Control of human PIRH2 protein stability: involvement of TIP60 and the proteosome, J. Biol. Chem. 279, 11696-11704   DOI   ScienceOn
109 Canning, M., C. Boutell, J. Parkinson, and R. D. Everett (2004), A RlNG finger ubiquitin ligase is protected from autocatalyzed ubiquitination and degradation by binding to ubiquitin-specific protease USP7, J. Biol. Chem. 279, 38160-38168   DOI   ScienceOn
110 Xu, P. and J. Peng (2008), Characterization of polyubiquitin chain structure by middle-down mass spectrometry, Anal. Chem. 80, 3438-3444   DOI   ScienceOn
111 Shaulsky, G., N. Goldfinger M. S. Tosky, A. J. Levine, and V. Rotter (1991), Nuclear localization is essential for the activity of p53 protein, Oncogene 6, 2055-2065   PUBMED   ScienceOn
112 Carter, S., O. Bischof, A. Dejean, and K. H. Vousden (2007), C-terminal modifications regulate MDM2 dissociation and nuclear export of p53, Nat. Cell Biol. 9, 428-435   DOI   ScienceOn
113 Diao, L., B. Zhang, J. Fan, X. Gao, S. Sun, K. Yang, D. Xin, N. Jin, Y. Geng, and C. Wang (2005), Herpes virus proteins ICP0 and BICP0 can activate NF-kappaB by catalyzing IkappaBalpha ubiquitination, Cell Signal. 17, 217-229   DOI   ScienceOn
114 Laine, A. and Z. Ronai (2007), Regulation of p53 localization and transcription by the HECT domain E3 ligase WWP1, Oncogene 26, 1477-1483   DOI   ScienceOn
115 McDonald, E. R. 3rd and W. S. EI-Deiry (2004), Suppression of caspase-8- and -10-associated RlNG proteins rεsults in sensitization to death ligands and inhibition of tumor cell growth, Proc. Natl. Acad. Sci. USA 101, 6170-6175   DOI   ScienceOn
116 Budhram-Mahadeo, V., P. J. Morris, M. D. Smith, C. A. Midgley, L. M. Boxer, and D. S. Latchman (1999), p53 suppresses the activation of the Bcl-2 promoter by the Bm-3a POU fami1y transcription factor, J. Biol. Chem. 274, 15237-15244   DOI   ScienceOn
117 O'Connor, M. J., H. Zimmerrnann, S. Nielsen, H. U. Bemard, and T. Kouzarides (1999), Characterization of an EIA-CBP intεraction defines a novel transcriptional adapter motif (TRAM) in CBP/p300, J. Virol. 73, 3574-3581   PUBMED   ScienceOn
118 Leng, R. P., Y. Lin, W. Ma, H. Wu, B. Lemmers, S. Chung, J. M. Parant, G. Lozano, R. Hakem, and S. Benchimol (2003), Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation, Cell 112, 779-791   DOI   ScienceOn
119 Yang, J. Y., C. S. Zong, W. Xia, H. Yamaguchi, Q. Ding, X. Xie, J. Y. Lang, C. C. Lai, C. J. Chang, W. C. Huang, H. Huang, H. P. Kuo, D. F. Lee, L. Y. Li, H. C. Lien, X. Cheng, K. J. Chang, C. D. Hsiao, F. J. Tsai, C. H. Tsai, A. A. Sahin, W. J. Muller, G. B. Mills, D. Yu, G. N. Hortobagyi, and M. C. Hung (2008), ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation, Nat. Cell Biol. 10, 138-148   DOI   ScienceOn