Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 300 (5617): 342-344

Copyright © 2003 by the American Association for the Advancement of Science

Polyubiquitination of p53 by a Ubiquitin Ligase Activity of p300

Steven R. Grossman,124* Maria E. Deato,1dagger Chrystelle Brignone,1* Ho Man Chan,1 Andrew L. Kung,135 Hideaki Tagami,1 Yoshihiro Nakatani,16 David M. Livingston147ddagger

Rapid turnover of the tumor suppressor protein p53 requires the MDM2 ubiquitin ligase, and both interact with p300-CREB-binding protein transcriptional coactivator proteins. p53 is stabilized by the binding of p300 to the oncoprotein E1A, suggesting that p300 regulates p53 degradation. Purified p300 exhibited intrinsic ubiquitin ligase activity that was inhibited by E1A. In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination. E1A expression caused a decrease in polyubiquitinated but not monoubiquitinated p53 in cells. Thus, generation of the polyubiquitinated forms of p53 that are targeted for proteasome degradation requires the intrinsic ubiquitin ligase activities of MDM2 and p300.

1 Department of Cancer Biology,
2 Department of Adult Oncology,
3 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
4 Department of Medicine,
5 Department of Pediatrics,
6 Department of Biological Chemistry and Molecular Pharmacology,
7 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
*   Present address: Department of Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.

dagger    Present address: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

ddagger    To whom correspondence should be addressed. E-mail: david_livingston{at}dfci.harvard.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
cAMP Response Element-Binding Protein Interacts With and Stimulates the Proteasomal Degradation of the Nuclear Receptor Coactivator GRIP1.
T. Hoang, I. S. Fenne, A. Madsen, O. Bozickovic, M. Johannessen, M. Bergsvag, E. A. Lien, M. R. Stallcup, J. V. Sagen, U. Moens, et al. (2013)
Endocrinology 154, 1513-1527
   Abstract »    Full Text »    PDF »
Role of Ubiquitin Ligases and the Proteasome in Oncogenesis: Novel Targets for Anticancer Therapies.
L. N. Micel, J. J. Tentler, P. G. Smith, and G. S. Eckhardt (2013)
J. Clin. Oncol. 31, 1231-1238
   Abstract »    Full Text »    PDF »
BRMS1 Suppresses Lung Cancer Metastases through an E3 Ligase Function on Histone Acetyltransferase p300.
Y. Liu, M. W. Mayo, A. S. Nagji, E. H. Hall, L. S. Shock, A. Xiao, E. B. Stelow, and D. R. Jones (2013)
Cancer Res. 73, 1308-1317
   Abstract »    Full Text »    PDF »
Stabilization of p53 in Influenza A Virus-infected Cells Is Associated with Compromised MDM2-mediated Ubiquitination of p53.
X. Wang, X. Deng, W. Yan, Z. Zhu, Y. Shen, Y. Qiu, Z. Shi, D. Shao, J. Wei, X. Xia, et al. (2012)
J. Biol. Chem. 287, 18366-18375
   Abstract »    Full Text »    PDF »
The Chaperone-assisted E3 Ligase C Terminus of Hsc70-interacting Protein (CHIP) Targets PTEN for Proteasomal Degradation.
S. F. Ahmed, S. Deb, I. Paul, A. Chatterjee, T. Mandal, U. Chatterjee, and M. K. Ghosh (2012)
J. Biol. Chem. 287, 15996-16006
   Abstract »    Full Text »    PDF »
E3Net: A System for Exploring E3-mediated Regulatory Networks of Cellular Functions.
Y. Han, H. Lee, J. C. Park, and G.-S. Yi (2012)
Mol. Cell. Proteomics 11, O111.014076
   Abstract »    Full Text »    PDF »
It Takes 15 to Tango: Making Sense of the Many Ubiquitin Ligases of p53.
I. M. Love and S. R. Grossman (2012)
Genes & Cancer 3, 249-263
   Abstract »    Full Text »    PDF »
Dual Roles of MDM2 in the Regulation of p53: Ubiquitination Dependent and Ubiquitination Independent Mechanisms of MDM2 Repression of p53 Activity.
D. Shi and W. Gu (2012)
Genes & Cancer 3, 240-248
   Abstract »    Full Text »    PDF »
The Regulation of Multiple p53 Stress Responses is Mediated through MDM2.
W. Hu, Z. Feng, and A. J. Levine (2012)
Genes & Cancer 3, 199-208
   Abstract »    Full Text »    PDF »
The Many Faces of MDM2 Binding Partners.
M. F. Riley and G. Lozano (2012)
Genes & Cancer 3, 226-239
   Abstract »    Full Text »    PDF »
Low-Dose Valproic Acid Enhances Radiosensitivity of Prostate Cancer through Acetylated p53-Dependent Modulation of Mitochondrial Membrane Potential and Apoptosis.
X. Chen, J. Y. C. Wong, P. Wong, and E. H. Radany (2011)
Mol. Cancer Res. 9, 448-461
   Abstract »    Full Text »    PDF »
Regulation of Glucocorticoid Receptor Activity by a Stress Responsive Transcriptional Cofactor.
L. Davies, E. Paraskevopoulou, M. Sadeq, C. Symeou, C. Pantelidou, C. Demonacos, and M. Krstic-Demonacos (2011)
Mol. Endocrinol. 25, 58-71
   Abstract »    Full Text »    PDF »
Graded enhancement of p53 binding to CREB-binding protein (CBP) by multisite phosphorylation.
C. W. Lee, J. C. Ferreon, A. C. M. Ferreon, M. Arai, and P. E. Wright (2010)
PNAS 107, 19290-19295
   Abstract »    Full Text »    PDF »
Turning the RING Domain Protein MdmX into an Active Ubiquitin-Protein Ligase.
S. Iyappan, H.-P. Wollscheid, A. Rojas-Fernandez, A. Marquardt, H.-C. Tang, R. K. Singh, and M. Scheffner (2010)
J. Biol. Chem. 285, 33065-33072
   Abstract »    Full Text »    PDF »
Transcriptional Regulation by P53.
R. Beckerman and C. Prives (2010)
Cold Spring Harb Perspect Biol 2, a000935
   Abstract »    Full Text »    PDF »
Transcriptional Synergy between Melanoma Antigen Gene Protein-A11 (MAGE-11) and p300 in Androgen Receptor Signaling.
E. B. Askew, S. Bai, A. J. Blackwelder, and E. M. Wilson (2010)
J. Biol. Chem. 285, 21824-21836
   Abstract »    Full Text »    PDF »
Complex Regulation of the Transactivation Function of Hypoxia-inducible Factor-1{alpha} by Direct Interaction with Two Distinct Domains of the CREB-binding Protein/p300.
J. L. Ruas, U. Berchner-Pfannschmidt, S. Malik, K. Gradin, J. Fandrey, R. G. Roeder, T. Pereira, and L. Poellinger (2010)
J. Biol. Chem. 285, 2601-2609
   Abstract »    Full Text »    PDF »
IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome.
L. M. Thompson, C. T. Aiken, L. S. Kaltenbach, N. Agrawal, K. Illes, A. Khoshnan, M. Martinez-Vincente, M. Arrasate, J. G. O'Rourke, H. Khashwji, et al. (2009)
J. Cell Biol. 187, 1083-1099
   Abstract »    Full Text »    PDF »
Posttranslational Modification of p53: Cooperative Integrators of Function.
D. W. Meek and C. W. Anderson (2009)
Cold Spring Harb Perspect Biol 1, a000950
   Abstract »    Full Text »    PDF »
Influence of zinc deficiency on Akt-Mdm2-p53 and Akt-p21 signaling axes in normal and malignant human prostate cells.
C.-T. Han, N. W. Schoene, and K. Y. Lei (2009)
Am J Physiol Cell Physiol 297, C1188-C1199
   Abstract »    Full Text »    PDF »
CBP and p300 are cytoplasmic E4 polyubiquitin ligases for p53.
D. Shi, M. S. Pop, R. Kulikov, I. M. Love, A. L. Kung, and S. R. Grossman (2009)
PNAS 106, 16275-16280
   Abstract »    Full Text »    PDF »
The Role of the Ubiquitin Proteasome System in Ischemia and Ischemic Tolerance.
R. Meller (2009)
Neuroscientist 15, 243-260
   Abstract »    PDF »
Influence of glutamine infusion on ubiquitin, caspase-3, cathepsins L and B, and m-calpain expression in sheep with nutritionally induced metabolic acidosis.
S. L. Greenwood, O. AlZahal, K. C. Swanson, J. C. Matthews, and B. W. McBride (2009)
J Anim Sci 87, 2073-2079
   Abstract »    Full Text »    PDF »
Cooperative regulation of p53 by modulation of ternary complex formation with CBP/p300 and HDM2.
J. C. Ferreon, C. W. Lee, M. Arai, M. A. Martinez-Yamout, H. J. Dyson, and P. E. Wright (2009)
PNAS 106, 6591-6596
   Abstract »    Full Text »    PDF »
Tax1BP1 Interacts with Papillomavirus E2 and Regulates E2-Dependent Transcription and Stability.
X. Wang, S. R. Naidu, F. Sverdrup, and E. J. Androphy (2009)
J. Virol. 83, 2274-2284
   Abstract »    Full Text »    PDF »
Hypoxia-Associated Factor, a Novel E3-Ubiquitin Ligase, Binds and Ubiquitinates Hypoxia-Inducible Factor 1{alpha}, Leading to Its Oxygen-Independent Degradation.
M. Y. Koh, B. G. Darnay, and G. Powis (2008)
Mol. Cell. Biol. 28, 7081-7095
   Abstract »    Full Text »    PDF »
Lysosomal Localization of Ubiquitinated Jun Requires Multiple Determinants in a Lysine-27-Linked Polyubiquitin Conjugate.
H. Ikeda and T. K. Kerppola (2008)
Mol. Biol. Cell 19, 4588-4601
   Abstract »    Full Text »    PDF »
MDM2 Regulates Dihydrofolate Reductase Activity through Monoubiquitination.
M. Maguire, P. C. Nield, T. Devling, R. E. Jenkins, B. K. Park, R. Polanski, N. Vlatkovic, and M. T. Boyd (2008)
Cancer Res. 68, 3232-3242
   Abstract »    Full Text »    PDF »
Identification of Ubiquitin Ligase Activity of RBCK1 and Its Inhibition by Splice Variant RBCK2 and Protein Kinase C{beta}.
K. Tatematsu, N. Yoshimoto, T. Okajima, K. Tanizawa, and S. Kuroda (2008)
J. Biol. Chem. 283, 11575-11585
   Abstract »    Full Text »    PDF »
Gp78 Cooperates with RMA1 in Endoplasmic Reticulum-associated Degradation of CFTR{Delta}F508.
D. Morito, K. Hirao, Y. Oda, N. Hosokawa, F. Tokunaga, D. M. Cyr, K. Tanaka, K. Iwai, and K. Nagata (2008)
Mol. Biol. Cell 19, 1328-1336
   Abstract »    Full Text »    PDF »
Critical and Functional Regulation of CHOP (C/EBP Homologous Protein) through the N-terminal Portion.
N. Ohoka, T. Hattori, M. Kitagawa, K. Onozaki, and H. Hayashi (2007)
J. Biol. Chem. 282, 35687-35694
   Abstract »    Full Text »    PDF »
A High-Throughput Screen Measuring Ubiquitination of p53 by Human mdm2.
M. F. Murray, A. J. Jurewicz, J. D. Martin, T. F. Ho, Hong Zhang, K. O. Johanson, R. B. Kirkpatrick, Jianhong Ma, L. A. Lor, S. H. Thrall, et al. (2007)
J Biomol Screen 12, 1050-1058
   Abstract »    PDF »
p300 expression repression by hypermethylation associated with tumour invasion and metastasis in oesophageal squamous cell carcinoma.
C. Zhang, K. Li, L. Wei, Z. Li, P. Yu, L. Teng, K. Wu, and J. Zhu (2007)
J. Clin. Pathol. 60, 1249-1253
   Abstract »    Full Text »    PDF »
Quantitative Profiling of Ubiquitylated Proteins Reveals Proteasome Substrates and the Substrate Repertoire Influenced by the Rpn10 Receptor Pathway.
T. Mayor, J. Graumann, J. Bryan, M. J. MacCoss, and R. J. Deshaies (2007)
Mol. Cell. Proteomics 6, 1885-1895
   Abstract »    Full Text »    PDF »
Stabilization of p53 in Human Cytomegalovirus-initiated Cells Is Associated with Sequestration of HDM2 and Decreased p53 Ubiquitination.
Z. Chen, E. Knutson, S. Wang, L. A. Martinez, and T. Albrecht (2007)
J. Biol. Chem. 282, 29284-29295
   Abstract »    Full Text »    PDF »
Negative regulation of the SH2-homology-containing protein-tyrosine phosphatase-1 (SHP-1) P2 promoter by the HTLV-1 Tax oncoprotein.
J. Cheng, A. R. Kydd, K. Nakase, K. M. Noonan, A. Murakami, H. Tao, M. Dwyer, C. Xu, Q. Zhu, and W. A. Marasco (2007)
Blood 110, 2110-2120
   Abstract »    Full Text »    PDF »
Induction of Cullin 7 by DNA damage attenuates p53 function.
P. Jung, B. Verdoodt, A. Bailey, J. R. Yates III, A. Menssen, and H. Hermeking (2007)
PNAS 104, 11388-11393
   Abstract »    Full Text »    PDF »
p300 Protein Acetyltransferase Activity Suppresses Systemic Lupus Erythematosus-Like Autoimmune Disease in Mice.
N. Forster, S. Gallinat, J. Jablonska, S. Weiss, H.-P. Elsasser, and W. Lutz (2007)
J. Immunol. 178, 6941-6948
   Abstract »    Full Text »    PDF »
p53 status dictates responses of B lymphomas to monotherapy with proteasome inhibitors.
D. Yu, M. Carroll, and A. Thomas-Tikhonenko (2007)
Blood 109, 4936-4943
   Abstract »    Full Text »    PDF »
Ubiquitin and Ubiquitin-Like Proteins in Protein Regulation.
J. Herrmann, L. O. Lerman, and A. Lerman (2007)
Circ. Res. 100, 1276-1291
   Abstract »    Full Text »    PDF »
PACT is a negative regulator of p53 and essential for cell growth and embryonic development.
L. Li, B. Deng, G. Xing, Y. Teng, C. Tian, X. Cheng, X. Yin, J. Yang, X. Gao, Y. Zhu, et al. (2007)
PNAS 104, 7951-7956
   Abstract »    Full Text »    PDF »
The N-terminal domain of the Aurora-A Phe-31 variant encodes an E3 ubiquitin ligase and mediates ubiquitination of I{kappa}B{alpha}.
P. Briassouli, F. Chan, and S. Linardopoulos (2006)
Hum. Mol. Genet. 15, 3343-3350
   Abstract »    Full Text »    PDF »
The Pure Estrogen Receptor Antagonist ICI 182,780 Promotes a Novel Interaction of Estrogen Receptor-{alpha} with the 3',5'-Cyclic Adenosine Monophosphate Response Element-Binding Protein-Binding Protein/p300 Coactivators.
B. M. Jaber, T. Gao, L. Huang, S. Karmakar, and C. L. Smith (2006)
Mol. Endocrinol. 20, 2695-2710
   Abstract »    Full Text »    PDF »
Genetic and Expression Aberrations of E3 Ubiquitin Ligases in Human Breast Cancer.
C. Chen, A. K. Seth, and A. E. Aplin (2006)
Mol. Cancer Res. 4, 695-707
   Abstract »    Full Text »    PDF »
Binding of p53 to the Central Domain of Mdm2 Is Regulated by Phosphorylation.
R. Kulikov, M. Winter, and C. Blattner (2006)
J. Biol. Chem. 281, 28575-28583
   Abstract »    Full Text »    PDF »
Regulation of the MDM2-p53 Pathway by Ribosomal Protein L11 Involves a Post-ubiquitination Mechanism.
M.-S. Dai, D. Shi, Y. Jin, X.-X. Sun, Y. Zhang, S. R. Grossman, and H. Lu (2006)
J. Biol. Chem. 281, 24304-24313
   Abstract »    Full Text »    PDF »
The Human Orthologue of Drosophila Ecdysoneless Protein Interacts with p53 and Regulates Its Function..
Y. Zhang, C. B. Gurumurthy, J. Kim, I. Bhat, Q. Gao, G. Dimri, S. W. Lee, H. Band, and V. Band (2006)
Cancer Res. 66, 7167-7175
   Abstract »    Full Text »    PDF »
Jab1 Induces the Cytoplasmic Localization and Degradation of p53 in Coordination with Hdm2.
W. Oh, E.-W. Lee, Y. H. Sung, M.-R. Yang, J. Ghim, H.-W. Lee, and J. Song (2006)
J. Biol. Chem. 281, 17457-17465
   Abstract »    Full Text »    PDF »
HSP27 favors ubiquitination and proteasomal degradation of p27Kip1 and helps S-phase re-entry in stressed cells.
A. Parcellier, M. Brunet, E. Schmitt, E. Col, C. Didelot, A. Hammann, K. Nakayama, K. I. Nakayama, S. Khochbin, E. Solary, et al. (2006)
FASEB J 20, 1179-1181
   Abstract »    Full Text »    PDF »
Nuclear Accumulations of p53 and Mdm2 Are Accompanied by Reductions in c-Abl and p300 in Zinc-Depleted Human Hepatoblastoma Cells.
A. A. Alshatwi, C.-T. Han, N. W. Schoene, and K. Y. Lei (2006)
Experimental Biology and Medicine 231, 611-618
   Abstract »    Full Text »    PDF »
Akt-Mediated Cisplatin Resistance in Ovarian Cancer: Modulation of p53 Action on Caspase-Dependent Mitochondrial Death Pathway..
X. Yang, M. Fraser, U. M. Moll, A. Basak, and B. K. Tsang (2006)
Cancer Res. 66, 3126-3136
   Abstract »    Full Text »    PDF »
Interferon-Inducible Protein IFIX{alpha}1 Functions as a Negative Regulator of HDM2.
Y. Ding, J.-F. Lee, H. Lu, M.-H. Lee, and D.-H. Yan (2006)
Mol. Cell. Biol. 26, 1979-1996
   Abstract »    Full Text »    PDF »
Overexpression of the Coactivator Bridge-1 Results in Insulin Deficiency and Diabetes.
J. L. Volinic, J. H. Lee, K. Eto, V. Kaur, and M. K. Thomas (2006)
Mol. Endocrinol. 20, 167-182
   Abstract »    Full Text »    PDF »
Ubiquitination of p53 at Multiple Sites in the DNA-Binding Domain.
W. M. Chan, M. C. Mak, T. K. Fung, A. Lau, W. Y. Siu, and R. Y.C. Poon (2006)
Mol. Cancer Res. 4, 15-25
   Abstract »    Full Text »    PDF »
p300 Modulates ATF4 Stability and Transcriptional Activity Independently of Its Acetyltransferase Domain.
I. Lassot, E. Estrabaud, S. Emiliani, M. Benkirane, R. Benarous, and F. Margottin-Goguet (2005)
J. Biol. Chem. 280, 41537-41545
   Abstract »    Full Text »    PDF »
Dual Regulation of c-Myc by p300 via Acetylation-Dependent Control of Myc Protein Turnover and Coactivation of Myc-Induced Transcription.
F. Faiola, X. Liu, S. Lo, S. Pan, K. Zhang, E. Lymar, A. Farina, and E. Martinez (2005)
Mol. Cell. Biol. 25, 10220-10234
   Abstract »    Full Text »    PDF »
Interactions with p300 enhance transcriptional activation by the PDZ-domain coactivator Bridge-1.
J. H Lee, J. L Volinic, C. Banz, K.-M. Yao, and M. K Thomas (2005)
J. Endocrinol. 187, 283-292
   Abstract »    Full Text »    PDF »
Role of the UBL-UBA Protein KPC2 in Degradation of p27 at G1 Phase of the Cell Cycle.
T. Hara, T. Kamura, S. Kotoshiba, H. Takahashi, K. Fujiwara, I. Onoyama, M. Shirakawa, N. Mizushima, and K. I. Nakayama (2005)
Mol. Cell. Biol. 25, 9292-9303
   Abstract »    Full Text »    PDF »
Cross Talk in Hormonally Regulated Gene Transcription through Induction of Estrogen Receptor Ubiquitylation.
M. Luo, M. Koh, J. Feng, Q. Wu, and P. Melamed (2005)
Mol. Cell. Biol. 25, 7386-7398
   Abstract »    Full Text »    PDF »
ING2 Regulates the Onset of Replicative Senescence by Induction of p300-Dependent p53 Acetylation.
R. Pedeux, S. Sengupta, J. C. Shen, O. N. Demidov, S. Saito, H. Onogi, K. Kumamoto, S. Wincovitch, S. H. Garfield, M. McMenamin, et al. (2005)
Mol. Cell. Biol. 25, 6639-6648
   Abstract »    Full Text »    PDF »
A Chromatin-associated and Transcriptionally Inactive p53-Mdm2 Complex Occurs in mdm2 SNP309 Homozygous Cells.
N. C. Arva, T. R. Gopen, K. E. Talbott, L. E. Campbell, A. Chicas, D. E. White, G. L. Bond, A. J. Levine, and J. Bargonetti (2005)
J. Biol. Chem. 280, 26776-26787
   Abstract »    Full Text »    PDF »
The Chaperone-associated Ubiquitin Ligase CHIP Is Able to Target p53 for Proteasomal Degradation.
C. Esser, M. Scheffner, and J. Hohfeld (2005)
J. Biol. Chem. 280, 27443-27448
   Abstract »    Full Text »    PDF »
Involvement of Nuclear Export in Human Papillomavirus Type 18 E6-Mediated Ubiquitination and Degradation of p53.
D. Stewart, A. Ghosh, and G. Matlashewski (2005)
J. Virol. 79, 8773-8783
   Abstract »    Full Text »    PDF »
p400 Is Required for E1A to Promote Apoptosis.
A. V. Samuelson, M. Narita, H.-M. Chan, J. Jin, E. de Stanchina, M. E. McCurrach, M. Narita, M. Fuchs, D. M. Livingston, and S. W. Lowe (2005)
J. Biol. Chem. 280, 21915-21923
   Abstract »    Full Text »    PDF »
Recruitment of CBP/p300, TATA-Binding Protein, and S8 to Distinct Regions at the N Terminus of Adenovirus E1A.
M. Rasti, R. J. A. Grand, J. S. Mymryk, P. H. Gallimore, and A. S. Turnell (2005)
J. Virol. 79, 5594-5605
   Abstract »    Full Text »    PDF »
Linking the ubiquitin-proteasome pathway to chromatin remodeling/modification by nuclear receptors.
H K Kinyamu, J Chen, and T K Archer (2005)
J. Mol. Endocrinol. 34, 281-297
   Abstract »    Full Text »    PDF »
SIRT1 Deacetylation and Repression of p300 Involves Lysine Residues 1020/1024 within the Cell Cycle Regulatory Domain 1.
T. Bouras, M. Fu, A. A. Sauve, F. Wang, A. A. Quong, N. D. Perkins, R. T. Hay, W. Gu, and R. G. Pestell (2005)
J. Biol. Chem. 280, 10264-10276
   Abstract »    Full Text »    PDF »
Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development.
W. J. Weninger, K. L. Floro, M. B. Bennett, S. L. Withington, J. I. Preis, J. P. M. Barbera, T. J. Mohun, and S. L. Dunwoodie (2005)
Development 132, 1337-1348
   Abstract »    Full Text »    PDF »
B56 Regulatory Subunit of Protein Phosphatase 2A Mediates Valproic Acid-Induced p300 Degradation.
J. Chen, J. R. St-Germain, and Q. Li (2005)
Mol. Cell. Biol. 25, 525-532
   Abstract »    Full Text »    PDF »
Effects of Depletion of CREB-binding Protein on c-Myc Regulation and Cell Cycle G1-S Transition.
H. N. Rajabi, S. Baluchamy, S. Kolli, A. Nag, R. Srinivas, P. Raychaudhuri, and B. Thimmapaya (2005)
J. Biol. Chem. 280, 361-374
   Abstract »    Full Text »    PDF »
Cul4A Physically Associates with MDM2 and Participates in the Proteolysis of p53.
A. Nag, S. Bagchi, and P. Raychaudhuri (2004)
Cancer Res. 64, 8152-8155
   Abstract »    Full Text »    PDF »
Inhibiting Proteasomal Proteolysis Sustains Estrogen Receptor-{alpha} Activation.
M. Fan, H. Nakshatri, and K. P. Nephew (2004)
Mol. Endocrinol. 18, 2603-2615
   Abstract »    Full Text »    PDF »
Enhanced Expression of Cell Cycle Regulatory Genes in Virus-Specific Memory CD8+ T Cells.
D. R. Latner, S. M. Kaech, and R. Ahmed (2004)
J. Virol. 78, 10953-10959
   Abstract »    Full Text »    PDF »
Topors Functions as an E3 Ubiquitin Ligase with Specific E2 Enzymes and Ubiquitinates p53.
R. Rajendra, D. Malegaonkar, P. Pungaliya, H. Marshall, Z. Rasheed, J. Brownell, L. F. Liu, S. Lutzker, A. Saleem, and E. H. Rubin (2004)
J. Biol. Chem. 279, 36440-36444
   Abstract »    Full Text »    PDF »
YY1 inhibits the activation of the p53 tumor suppressor in response to genotoxic stress.
E. Gronroos, A. A. Terentiev, T. Punga, and J. Ericsson (2004)
PNAS 101, 12165-12170
   Abstract »    Full Text »    PDF »
Herpes Simplex Virus Type 1 Infection Induces the Stabilization of p53 in a USP7- and ATM-Independent Manner.
C. Boutell and R. D. Everett (2004)
J. Virol. 78, 8068-8077
   Abstract »    Full Text »    PDF »
E1B-55-Kilodalton Protein Is Not Required To Block p53-Induced Transcription during Adenovirus Infection.
U. Hobom and M. Dobbelstein (2004)
J. Virol. 78, 7685-7697
   Abstract »    Full Text »    PDF »
Transforming Growth Factor-{beta} Stimulates p300-dependent RUNX3 Acetylation, Which Inhibits Ubiquitination-mediated Degradation.
Y.-H. Jin, E.-J. Jeon, Q.-L. Li, Y. H. Lee, J.-K. Choi, W.-J. Kim, K.-Y. Lee, and S.-C. Bae (2004)
J. Biol. Chem. 279, 29409-29417
   Abstract »    Full Text »    PDF »
Multiple Interactions of Rad23 Suggest a Mechanism for Ubiquitylated Substrate Delivery Important in Proteolysis.
I. Kim, K. Mi, and H. Rao (2004)
Mol. Biol. Cell 15, 3357-3365
   Abstract »    Full Text »    PDF »
The Targeting of the Proteasomal Regulatory Subunit S2 by Adenovirus E1A Causes Inhibition of Proteasomal Activity and Increased p53 Expression.
X. Zhang, A. S. Turnell, C. Gorbea, J. S. Mymryk, P. H. Gallimore, and R. J. A. Grand (2004)
J. Biol. Chem. 279, 25122-25133
   Abstract »    Full Text »    PDF »
p300 regulates p53-dependent apoptosis after DNA damage in colorectal cancer cells by modulation of PUMA/p21 levels.
N. G. Iyer, S.-F. Chin, H. Ozdag, Y. Daigo, D.-E. Hu, M. Cariati, K. Brindle, S. Aparicio, and C. Caldas (2004)
PNAS 101, 7386-7391
   Abstract »    Full Text »    PDF »
MDM2 Mediates p300/CREB-binding Protein-associated Factor Ubiquitination and Degradation.
Y. Jin, S. X. Zeng, H. Lee, and H. Lu (2004)
J. Biol. Chem. 279, 20035-20043
   Abstract »    Full Text »    PDF »
TSG101 Interacts with Apoptosis-antagonizing Transcription Factor and Enhances Androgen Receptor-mediated Transcription by Promoting Its Monoubiquitination.
S. Burgdorf, P. Leister, and K. H. Scheidtmann (2004)
J. Biol. Chem. 279, 17524-17534
   Abstract »    Full Text »    PDF »
Control of Human PIRH2 Protein Stability: INVOLVEMENT OF TIP60 AND THE PROTEASOME.
I. R. Logan, V. Sapountzi, L. Gaughan, D. E. Neal, and C. N. Robson (2004)
J. Biol. Chem. 279, 11696-11704
   Abstract »    Full Text »    PDF »
Participation of the Ubiquitin-Conjugating Enzyme UBE2E3 in Nedd4-2-Dependent Regulation of the Epithelial Na+ Channel.
C. Debonneville and O. Staub (2004)
Mol. Cell. Biol. 24, 2397-2409
   Abstract »    Full Text »    PDF »
Regulation of p53 Stability and Function in HCT116 Colon Cancer Cells.
M. D. Kaeser, S. Pebernard, and R. D. Iggo (2004)
J. Biol. Chem. 279, 7598-7605
   Abstract »    Full Text »    PDF »
Coregulator Function: A Key to Understanding Tissue Specificity of Selective Receptor Modulators.
C. L. Smith and B. W. O'Malley (2004)
Endocr. Rev. 25, 45-71
   Abstract »    Full Text »    PDF »
Making Sense of Cross-Talk between Steroid Hormone Receptors and Intracellular Signaling Pathways: Who Will Have the Last Word?.
C. A. Lange (2004)
Mol. Endocrinol. 18, 269-278
   Abstract »    Full Text »    PDF »
Mdm2 in the Response to Radiation.
M. E. Perry (2004)
Mol. Cancer Res. 2, 9-19
   Abstract »    Full Text »    PDF »
The Co-repressor Hairless Protects ROR{alpha} Orphan Nuclear Receptor from Proteasome-mediated Degradation.
A. N. Moraitis and V. Giguere (2003)
J. Biol. Chem. 278, 52511-52518
   Abstract »    Full Text »    PDF »
Defective p53 Post-translational Modification Required for Wild Type p53 Inactivation in Malignant Epithelial Cells with mdm2 Gene Amplification.
C. D. Knights, Y. Liu, E. Appella, and M. Kulesz-Martin (2003)
J. Biol. Chem. 278, 52890-52900
   Abstract »    Full Text »    PDF »
Involvement of the DNA Repair Protein hHR23 in p53 Degradation.
S. Glockzin, F.-X. Ogi, A. Hengstermann, M. Scheffner, and C. Blattner (2003)
Mol. Cell. Biol. 23, 8960-8969
   Abstract »    Full Text »    PDF »
Mono- Versus Polyubiquitination: Differential Control of p53 Fate by Mdm2.
M. Li, C. L. Brooks, F. Wu-Baer, D. Chen, R. Baer, and W. Gu (2003)
Science 302, 1972-1975
   Abstract »    Full Text »    PDF »
The Proline Repeat Domain of p53 Binds Directly to the Transcriptional Coactivator p300 and Allosterically Controls DNA-Dependent Acetylation of p53.
D. Dornan, H. Shimizu, L. Burch, A. J. Smith, and T. R. Hupp (2003)
Mol. Cell. Biol. 23, 8846-8861
   Abstract »    Full Text »    PDF »
Ribosomal Protein L11 Negatively Regulates Oncoprotein MDM2 and Mediates a p53-Dependent Ribosomal-Stress Checkpoint Pathway.
Y. Zhang, G. W. Wolf, K. Bhat, A. Jin, T. Allio, W. A. Burkhart, and Y. Xiong (2003)
Mol. Cell. Biol. 23, 8902-8912
   Abstract »    Full Text »    PDF »
MDM2, An Introduction.
T. Iwakuma and G. Lozano (2003)
Mol. Cancer Res. 1, 993-1000
   Abstract »    Full Text »    PDF »
The MDM2-p53 Interaction.
U. M. Moll and O. Petrenko (2003)
Mol. Cancer Res. 1, 1001-1008
   Abstract »    Full Text »    PDF »
Cell Cycle Regulatory Functions of the Human Oncoprotein MDM2.
S. P. Deb (2003)
Mol. Cancer Res. 1, 1009-1016
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882