ProtModification Mdm2 ---| Tp53

URN urn:agi-ProtModification:inout-urn:agi-llid:4193:out-urn:agi-llid:7157::negative:ubiquitination
References 100
Connectivity 2
Effect negative
Mechanism ubiquitination
Original # of References 122

TextRef info:pmid/19880522#abs:10
PubYear 2010
MedlineTA J Biol Chem
MedLine Reference 19880522:9
Sentence Pyk2 FERM promoted Mdm2-dependent p53 ubiquitination.
CellType Fibroblasts

TextRef info:pmid/20124408#abs:8
PubYear 2010
MedlineTA J Biol Chem
MedLine Reference 20124408:7
Sentence In addition to reactivating mutant p53, SCH529074 binding inhibits ubiquitination of p53 by HDM2.

TextRef info:pmid/17585950#abs:5
PubYear 2007
MedlineTA Math Biosci
MedLine Reference 17585950:4
Sentence The model predicts existence of the HAUSP-regulated switch from auto- to p53 ubiquitination by Mdm2.

TextRef info:pmid/12860999#abs:2
PubYear 2003
MedlineTA Mol Cell Biol
MedLine Reference 12860999:1
Sentence Mitogenic signals activate p53 by induction of ARF expression, which inhibits p53 ubiquitination by MDM2.

TextRef info:pmid/19756449#abs:3
PubYear 2009
MedlineTA J Mol Med
MedLine Reference 19756449:2
Sentence In the present paper, we demonstrate that Sgk1 activates MDM2-dependent p53 ubiquitylation.
Tissue Serum

TextRef info:pmid/12690203#abs:3
PubYear 2003
MedlineTA Science
MedLine Reference 12690203:2
Sentence In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination.

TextRef info:pmid/17500067#abs:3
PubYear 2007
MedlineTA J Biol Chem
MedLine Reference 17500067:2
Sentence In addition to proteasome-mediated degradation, ubiquitination of p53 by Mdm2 acts a key signal for its nuclear export.

TextRef info:pmid/11960383#abs:1
PubYear 2002
MedlineTA Oncogene
MedLine Reference 11960383:0
Sentence Mutation of four lysine residues in the p53 C-terminal domain inhibits MDM2-dependent ubiquitination of p53 and alters its subcellular distribution.

TextRef info:pmid/11707453#abs:2
PubYear 2002
MedlineTA J Biol Chem
MedLine Reference 11707453:1
Sentence Following DNA damage or cellular stress, p53 is phosphorylated within the Mdm2 binding domain on threonine 18 and serine 20.

TextRef info:pmid/16857591#abs:1
PubYear 2006
MedlineTA Mol Cell
MedLine Reference 16857591:0
Sentence The control of p53 ubiquitination by MDM2 provides a model system to define how an E3-ligase functions on a conformationally flexible substrate.

TextRef info:pmid/12407176#abs:1
PubYear 2002
MedlineTA Proc Natl Acad Sci U S A
MedLine Reference 12407176:0
Sentence The oncoprotein hdm2 ubiquitinates p53, resulting in the rapid degradation of p53 through the ubiquitin -proteasome pathway.
TextMods 104: '(Ub)' -> ''

TextRef info:pmid/17237821#abs:5
PubYear 2007
MedlineTA Oncogene
MedLine Reference 17237821:4
Sentence In the present study, we show that TAFII250 stimulates the ubiquitylation and degradation of p53 in a manner that is dependent upon Mdm2 and requires its acidic domain.

TextRef info:pmid/11127820#abs:7
PubYear 2000
MedlineTA Oncogene
MedLine Reference 11127820:6
Sentence In addition, an MDM2-mutant that localized to the cytoplasm was able to ubiquitinate and degrade a p53 mutant which was similarly localized in the cytoplasm.

TextRef info:pmid/12426395#abs:4
PubYear 2002
MedlineTA EMBO J
MedLine Reference 12426395:3
Sentence Ectopic expression of a dominant-negative HDAC1 mutant restores p53 acetylation in the presence of MDM2, whereas wild-type HDAC1 and MDM2 deacetylate p53 synergistically.

TextRef info:pmid/15542844#abs:8
PubYear 2004
MedlineTA Mol Cell Biol
MedLine Reference 15542844:7
Sentence VRK1 phosphorylates human p53 in Thr18 and disrupts p53-Mdm2 interaction in vitro, although a significant decrease in p53 ubiquitination by Mdm2 in vivo was not detected.

TextRef info:pmid/20303977#abs:1
PubYear 2010
MedlineTA J Mol Biol
MedLine Reference 20303977:0
Sentence The multidomain E3 ubiquitin ligase MDM2 catalyzes p53 ubiquitination by a "dual-site" docking mechanism whereby MDM2 binding to at least two distinct peptide motifs on p53 promotes ubiquitination.

TextRef info:pmid/11925449#abs:5
PubYear 2002
MedlineTA J Biol Chem
MedLine Reference 11925449:4
Sentence Mutation of conserved amino acids in the linker at Ser(261) and Leu(264), which bridges the S9-S10 beta-sheets, stimulated p53 activity from reporter templates and increased MDM2-dependent ubiquitination of p53.

TextRef info:pmid/11779115#abs:3
PubYear 2002
MedlineTA Anal Biochem
MedLine Reference 11779115:2
Sentence One mechanism of regulating the amount of p53 in the cell is through the action of the Double Minute 2 protein, DM2 (also known as MDM2), which ubiquitinates p53 and targets it for proteosomal degradation.

TextRef info:pmid/19217357#abs:5
PubYear 2009
MedlineTA DNA Repair (Amst)
MedLine Reference 19217357:4
Sentence In this review we summarize current understanding on p53 ubiquitination by Mdm2 with a particular focus on how the balance between protein levels and other post-translational modifications will direct the p53 response.

TextRef info:pmid/17989425#abs:9
PubYear 2007
MedlineTA J Biomol Screen
MedLine Reference 17989425:8
Sentence The authors describe the development, validation, and execution of a high-throughput screening measuring the ubiquitination of p53 by mdm2, with p53 labeled with europium and the other substrate (Ub-UbcH5b) labeled with a Cy5 on the ubiquitin.

TextRef info:pmid/18333294#abs:8
PubYear 2008
MedlineTA Cell Cycle
MedLine Reference 18333294:7
Sentence We have recently shown that Wip1, also a p53 target gene, dephosphorylates Mdm2 at Ser395 (an ATM target site), resulting in stabilization of Mdm2, enhanced Mdm2-p53 binding, and enhanced ubiquitination of p53 by Mdm2.

TextRef info:pmid/17369817#abs:2
PubYear 2007
MedlineTA Nat Cell Biol
MedLine Reference 17369817:1
Sentence One of the most important regulators of p53 is MDM2, a RING domain E3 ligase that ubiquitinates p53, leading to both proteasomal degradation and relocation of p53 from the nucleus to the cytoplasm.

TextRef info:pmid/19303885#abs:8
PubYear 2009
MedlineTA J Mol Biol
MedLine Reference 19303885:7
Sentence Thus, the results presented here for the first time highlight the role of SMAR1 in masking the active phosphorylation site of p53, enabling the deacetylation of p53 by HDAC1-MDM2 complex, thereby regulating the p53 transcriptional response during stress rescue.

TextRef info:pmid/20657550#abs:1
PubYear 2010
MedlineTA EMBO J
MedLine Reference 20657550:0
Sentence p53 mediates DNA damage-induced cell-cycle arrest, apoptosis, or senescence, and it is controlled by Mdm2, which mainly ubiquitinates p53 in the nucleus and promotes p53 nuclear export and degradation.

TextRef info:pmid/19202598#abs:4
PubYear 2008
MedlineTA Ernst Schering Found Symp Proc
MedLine Reference 19202598:3
Sentence Notably, recent studies indicate that both the stability and the subcellular localization of p53 are tightly regulated by ubiquitination; p53 is mainly ubiquitinated by Mdm2 but other ubiquitin ligases such as ARF-BP1/HectH9/MULE are also involved in p53 regulation in vivo.

TextRef info:pmid/15946545#abs:5
PubYear 2005
MedlineTA Zhonghua Zhong Liu Za Zhi
MedLine Reference 15946545:4
Sentence p53KRKKK-GFP was located in cytoplasm, and was not degraded by either MDM2 or MDM2-nuclear localization signal mutation, but could be ubiquitinated; p53KRKKK-nuclear localization signal-GFP could be brought back to nucleus by SV-40 nuclear localization signal, so could be both degraded and ubiquitinated by either MDM2 or MDM2-nuclear localization signal; Wild type p53 and mutant nuclear localization signal could be ubiquitinated by either wild type MDM2 or mutant nuclear localization signal.
TextMods 83: 'NLS ' -> 'nuclear localization signal ' 158: 'NLS' -> 'nuclear localization signal' 232: 'NLS' -> 'nuclear localization signal' 328: 'NLS' -> 'nuclear localization signal' 382: 'NLS ' -> 'nuclear localization signal ' 468: 'NLS' -> 'nuclear locali...

TextRef info:pmid/9878046#body:47
PubYear 1999
MedlineTA EMBO J
MedLine Reference 9878046:1046
Sentence Ubiquitination of wild-type p53 by Mdm2 .

TextRef info:pmid/16446403#body:115
PubYear 2006
MedlineTA Mol Cancer Res
MedLine Reference 16446403:1114
Sentence MDM2-dependent p53 ubiquitination and degradation assays.

TextRef info:pmid/12586367#title:1
PubYear 2003
MedLine Reference 12586367:100
Sentence Differences in the ubiquitination of p53 by Mdm2 and the HPV protein E6.

TextRef info:pmid/18234968#body:191
PubYear 2008
MedlineTA Mol Cancer Res
MedLine Reference 18234968:1190
Sentence SS18-SSX1-induced p53 ubiquitination is dependent on HDM2.

TextRef info:pmid/15122315#body:193
PubYear 2004
MedlineTA Oncogene
MedLine Reference 15122315:1192
Sentence Thus, only in HIPK2-interfered cells p53 is ubiquitinated by MDM2.

TextRef info:pmid/11807090#body:266
PubYear 2002
MedlineTA J Cell Biol
MedLine Reference 11807090:1265
Sentence MDM2 ubiquitinates itself as well as p53 (Fang et al., 2000).
Organ Fingers

TextRef info:pmid/16023600#body:221
PubYear 2005
MedlineTA Cancer Cell
MedLine Reference 16023600:1220
Sentence Gankyrin enhances the Mdm2-dependent ubiquitylation of p53 .
Organ Fingers

TextRef info:pmid/11486026#body:343
PubYear 2001
MedlineTA Mol Cell Biol
MedLine Reference 11486026:1342
Sentence How does c-Abl impair the ubiquitination of p53 by E6-E6-AP and by Mdm2?

TextRef info:pmid/15577944#body:126
PubYear 2005
MedlineTA EMBO J
MedLine Reference 15577944:1125
Sentence Ubiquitination of p53 by Mdm2 was also negatively regulated by ARF in vivo (data not shown).

TextRef info:pmid/11250899#body:160
PubYear 2001
MedlineTA EMBO J
MedLine Reference 11250899:1159
Sentence Fig. 5. p19ARF reverses the inhibition of p53 acetylation by MDM2.
CellLineName H1299

TextRef info:pmid/19147532#body:211
PubYear 2009
MedlineTA Mol Cancer Res
MedLine Reference 19147532:1210
Sentence Additional strategies to prevent Mdm2-dependent ubiquitination of p53 have also been explored.

TextRef info:pmid/15021897#body:224
PubYear 2004
MedlineTA Oncogene
MedLine Reference 15021897:1223
Sentence One attractive strategy to inhibit ubiquitination of p53 by Mdm2 is to block their interaction.

TextRef info:pmid/14757841#body:339
PubYear 2004
MedlineTA Mol Cancer Res
MedLine Reference 14757841:1338
Sentence Moreover, ubiquitination of p53 by Mdm2 is not sufficient to catalyze its degradation (99, 100).

TextRef info:pmid/14707282#body:58
PubYear 2003
MedlineTA Mol Cancer Res
MedLine Reference 14707282:1057
Sentence MDM2 functions as the E3 ligase to ubiquitinate p53 at several lysine residues (10, 11).

TextRef info:pmid/14612427#body:152
PubYear 2003
MedlineTA Mol Cell Biol
MedLine Reference 14612427:1151
Sentence HDM2 functions as an E3 ligase to ubiquitinate p53 and promotes p53 degradation (11).

TextRef info:pmid/10626788#body:215
PubYear 1999
MedlineTA Cancer Res
MedLine Reference 10626788:1214
Sentence Thus, p53 phosphorylation may inhibit the efficient ubiquitination of p53 by residual MDM2 protein.

TextRef info:pmid/11313871#body:159
PubYear 2001
MedlineTA Oncogene
MedLine Reference 11313871:1158
Sentence MDM2 possess E3 ligase activity and catalyses its own and p53 ubiquitylation (Fang et al., 2000).

TextRef info:pmid/16107876#body:270
PubYear 2005
MedlineTA EMBO J
MedLine Reference 16107876:1269
Sentence Ubiquitination of p53 by MDM2 is a major mechanism by which p53 level is regulated in the cell.
CellLineName HT 1080

TextRef info:pmid/15604276#body:228
PubYear 2004
MedlineTA Cancer Res
MedLine Reference 15604276:1227
Sentence Interestingly, the authors observed that E1A stabilizes p53 without interfering p53 ubiquitination by Mdm2 (27) .

TextRef info:pmid/14612423#body:230
PubYear 2003
MedlineTA Mol Cell Biol
MedLine Reference 14612423:1229
Sentence The effects of the LXXLL and PXXP-GFP fusion proteins on MDM2-dependent ubiquitination of p53 were also examined (Fig. 4G).

TextRef info:pmid/12370303#body:236
PubYear 2002
MedlineTA Mol Cell Biol
MedLine Reference 12370303:1235
Sentence This inhibitory effect may not be directly reversed by ARF, since ARF mainly acts by inhibiting p53 ubiquitination by MDM2.

TextRef info:pmid/16636310#body:66
PubYear 2006
MedlineTA Exp Biol Med (Maywood)
MedLine Reference 16636310:1065
Sentence Although Mdm2 catalyzes p53 monoubiquitination (12), the product is not a substrate for proteasome degradation.

TextRef info:pmid/16024788#body:67
PubYear 2005
MedlineTA Mol Cell Biol
MedLine Reference 16024788:1066
Sentence Interestingly, ARF inhibits the ability of MDM2 to ubiquitinate p53 but stimulates MDM2 ubiquitination of MDMX (31).

TextRef info:pmid/12202042#title:1
PubYear 2002
MedLine Reference 12202042:100
Sentence SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53.

TextRef info:pmid/10892746#title:1
PubYear 2000
MedLine Reference 10892746:100
Sentence SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53.

TextRef info:pmid/16163388#body:66
PubYear 2005
MedlineTA EMBO J
MedLine Reference 16163388:1065
Sentence ARF inhibits the ability of MDM2 to ubiquitinate p53, but stimulates MDM2 ubiquitination of MDMX (Pan and Chen, 2003).

TextRef info:pmid/11744695#body:141
PubYear 2002
MedlineTA J Biol Chem
MedLine Reference 11744695:1140
Sentence In these conditions, Hdmx did not detectably change the overall pattern of Hdm2-dependent ubiquitination of p53.
Organ Fingers

TextRef info:pmid/17908790#body:230
PubYear 2007
MedlineTA Mol Cell Biol
MedLine Reference 17908790:1229
Sentence Our results so far showed that Mdm2 ubiquitinated mutant p53 less efficiently than wild-type p53 in vitro.
CellType Fibroblasts

TextRef info:pmid/15775960#body:216
PubYear 2005
MedlineTA EMBO J
MedLine Reference 15775960:1215
Sentence In the presence of Mdm2, there is a dramatic increase in the levels of NEDDylated and ubiquitinated p53 (Figure 5).
CellLineName H1299

TextRef info:pmid/12493762#body:59
PubYear 2003
MedlineTA J Biol Chem
MedLine Reference 12493762:1058
Sentence MDM2 possesses an E3-like ubiquitin ligase activity and thus ubiquitinates p53 (25), leading to its degradation (26, 27).

TextRef info:pmid/11046142#body:193
PubYear 2000
MedlineTA Mol Cell Biol
MedLine Reference 11046142:1192
Sentence Glutathione S-transferase (more ...). p53 C-terminal lysine residues are targets for Mdm2-dependent ubiquitination of p53.
TextMods 0: 'GST ' -> 'Glutathione S-transferase '

TextRef info:pmid/17098746#body:223
PubYear 2007
MedlineTA J Biol Chem
MedLine Reference 17098746:1222
Sentence Mdm2 ubiquitinates p53 on six C-terminal lysines and targets it to the proteasome for degradation (4, 5).
CellLineName H1299

TextRef info:pmid/16455486#body:91
PubYear 2006
MedlineTA Mol Cell
MedLine Reference 16455486:1090
Sentence Mdm2 was recently found to differentially catalyze monoubiquitination and polyubiquitination of p53 in a dosage-dependent manner (Li et al., 2003).

TextRef info:pmid/12509446#body:39
PubYear 2003
MedlineTA Mol Cell Biol
MedLine Reference 12509446:1038
Sentence In addition, p90 MDM2 ubiquitinates p53, stimulating its export from the nucleus (8, 50) as well as its degradation (15, 18, 27).

TextRef info:pmid/17015431#body:48
PubYear 2006
MedlineTA Genes Dev
MedLine Reference 17015431:1047
Sentence Furthermore, ubiquitination of p53 by Mdm2 expels p53 from the nucleus, keeping it away from its transcriptional targets.

TextRef info:pmid/15053880#body:66
PubYear 2004
MedlineTA Mol Cell
MedLine Reference 15053880:1065
Sentence DNA Repair [Close]. [You are not entitled to access the full text of this document] p53 ubiquitination by Mdm2: A never ending tail?

TextRef info:pmid/14654783#body:242
PubYear 2003
MedlineTA Oncogene
MedLine Reference 14654783:1241
Sentence In fact, Mdm2-dependent multiple monoubiquitination of p53 is responsible for its nuclear export (Gu et al., 2001; Lohrum et al., 2001).
Organ Fingers

TextRef info:pmid/16805769#body:86
PubYear 2006
MedlineTA J Neurochem
MedLine Reference 16805769:1085
Sentence This degradation is largely regulated by Mdm2, an E3 ubiquitin ligase that binds to and ubiquitinates p53, thus targeting it for degradation.

TextRef info:pmid/12421820#body:107
PubYear 2002
MedlineTA J Biol Chem
MedLine Reference 12421820:1106
Sentence To provide the direct evidence that acetylation of p53 affects its ubiquitination, we set up a reconstitution system for p53 ubiquitination by Mdm2.

TextRef info:pmid/19648273#body:70
PubYear 2009
MedlineTA J Immunol
MedLine Reference 19648273:1069
Sentence Additionally, as an E3 ligase, MDM2 ubiquitinates p53, inducing its nuclear export and proteosomal degradation (21, 22).
CellType B-Lymphocytes
Organ germinal center of lymph node

TextRef info:pmid/15888490#body:137
PubYear 2005
MedlineTA Carcinogenesis
MedLine Reference 15888490:1136
Sentence Ubiquitination of p53 by Mdm2, therefore, appears to have two roles, targeting of p53 to the proteasome for degradation and nuclear export.

TextRef info:pmid/12917636#body:54
PubYear 2003
MedlineTA Oncogene
MedLine Reference 12917636:1053
Sentence Therefore, the C-terminal region of ARF including the nucleolar localization signal is not essential for regulation of p53 ubiquitination by MDM2.
TextMods 54: 'NoLS ' -> 'nucleolar localization signal '

TextRef info:pmid/12802279#body:42
PubYear 2003
MedlineTA Oncogene
MedLine Reference 12802279:1041
Sentence Under normal conditions, Mdm2, which possesses E3 ubiquitin ligase activity, ubiquitinates and targets nuclear p53 for degradation (Vousden et al., 2000).

TextRef info:pmid/17429071#body:337
PubYear 2007
MedlineTA Mol Biol Cell
MedLine Reference 17429071:1336
Sentence These observations have clearly demonstrated that TGF-β resistance can be uncoupled with the ability of MDM2 to ubiquitinate and degrade p53.
Organ Fingers

TextRef info:pmid/14707283#body:70
PubYear 2003
MedlineTA Mol Cancer Res
MedLine Reference 14707283:1069
Sentence In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 alone only catalyzed p53 monoubiquitination.
Organ Fingers

TextRef info:pmid/18483214#body:78
PubYear 2008
MedlineTA Genes Dev
MedLine Reference 18483214:1077
Sentence On the other hand, Mdm2 has been reported to ubiquitinate and degrade tumor-derived mutant forms of p53 (Midgley and Lane 1997; Shimizu et al. 2006).

TextRef info:pmid/17170702#body:134
PubYear 2007
MedlineTA EMBO J
MedLine Reference 17170702:1133
Sentence As a positive control, p53 was ubiquitinated by MDM2 in an in vivo ubiquitination assay (Figure 5C) (Haupt et al, 1997; Kubbutat et al, 1997). [Figure 5].
Organ Fingers

TextRef info:pmid/18206965#body:120
PubYear 2008
MedlineTA Mol Cell
MedLine Reference 18206965:1119
Sentence We show that FAK inactivates p53 in a kinase-independent manner via the FAK FERM domain acting as a scaffold to enhance Mdm2-dependent p53 ubiquitination.

TextRef info:pmid/11711428#body:37
PubYear 2001
MedlineTA Genes Dev
MedLine Reference 11711428:1036
Sentence The best characterized negative regulator of p53 is Mdm2, which ubiquitinates p53 and targets its proteolytic destruction (Prives 1998;Juven-Gershon and Oren 1999).

TextRef info:pmid/18566590#body:225
PubYear 2008
MedlineTA EMBO J
MedLine Reference 18566590:1224
Sentence Intriguingly, the balance between self- and p53-ubiquitinating activities of MDM2 can be regulated by the combined actions of DAXX and HAUSP (Tang et al, 2006).

TextRef info:pmid/17875722#body:67
PubYear 2007
MedlineTA Cancer Res
MedLine Reference 17875722:1066
Sentence However, MDMX forms heterodimers with MDM2 through COOH-terminal RING domain interactions, which stimulates the ability of MDM2 to ubiquitinate and degrade p53 (10-13).

TextRef info:pmid/11070080#body:224
PubYear 2000
MedlineTA Proc Natl Acad Sci U S A
MedLine Reference 11070080:1223
Sentence By this rationale, inhibition of p300-mediated p53 acetylation by MDM2 would result in more efficient ubiquitination, consequently leading to the degradation of p53.

TextRef info:pmid/12612087#body:234
PubYear 2003
MedlineTA Mol Cell Biol
MedLine Reference 12612087:1233
Sentence MDM2 binds to the N-terminal transactivation domain of p53 with its p53-binding domain, and the RING domain of MDM2 catalyses the ubiquitination of p53 (13).

TextRef info:pmid/11175334#body:144
PubYear 2000
MedlineTA Oncogene
MedLine Reference 11175334:1143
Sentence Mdm-2 may contribute to this process by ubiquitinating p53 in vivo, since Mdm-2 can act as a ubiquitin ligase ES for p53 in vitro (Honda et al., 1997).
CellLineName BV-173

TextRef info:pmid/12232053#body:161
PubYear 2002
MedlineTA Proc Natl Acad Sci U S A
MedLine Reference 12232053:1160
Sentence The tumor suppressor p53 is a short-lived protein that accumulates after different stress signals that decrease the ability of Mdm-2 to ubiquitinate p53.
CellType thymocytes
Organ Bone Marrow

TextRef info:pmid/19033443#body:261
PubYear 2009
MedlineTA J Biol Chem
MedLine Reference 19033443:1260
Sentence Ubiquitination assays show that although both Mdm2 and MSL2 are able to ubiquitinate wild type p53 (Fig. 8B, lanes 3 and 4), only MSL2 is able to ubiquitinate p53Q22/23S (Fig. 8B, lane 7).
TextMods 159: 'p53QS ' -> 'p53Q22/23S '

TextRef info:pmid/20348954#body:190
PubYear 2010
MedlineTA Oncogene
MedLine Reference 20348954:1189
Sentence MDM2 is one of the E3 ligases in the ubiquitin-proteasome system and is known to ubiquitinate and degrade p53 tumor suppressor.
Tissue Blood
Organ Gastrointestinal tract

TextRef info:pmid/18172009#body:58
PubYear 2008
MedlineTA Mol Cell Biol
MedLine Reference 18172009:1057
Sentence MDMX forms heterodimers with MDM2 through C-terminal RING domain interactions (40, 47), which stimulates the ability of MDM2 to ubiquitinate and degrade p53 (16, 26).
CellType Fibroblasts
Organism Mus musculus

TextRef info:pmid/16227412#body:159
PubYear 2005
MedlineTA Mol Cancer Ther
MedLine Reference 16227412:1158
Sentence Western blot analysis showed distinctly elevated levels of p53, p53 phosphorylated on Ser15, and MDM2 as early as 3 hours after the initiation of treatment with WMC-79.
CellLineName RKO

TextRef info:pmid/16023592#body:66
PubYear 2005
MedlineTA Cancer Cell
MedLine Reference 16023592:1065
Sentence Compelling data are provided showing that this interaction occurs naturally between endogenous gankyrin and MDM2 and that gankyrin enhances the ability of MDM2 to ubiquitinate p53.

TextRef info:pmid/11593391#body:79
PubYear 2001
MedlineTA Oncogene
MedLine Reference 11593391:1078
Sentence For example, direct modification of p90 MDM2 by the small protein SUMO-1 has been shown to reduce p90 MDM2's ability to ubiquitinate p53 (Buschmann et al., 2000).
CellType Fibroblasts
Organism Homo sapiens

TextRef info:pmid/11331246#body:275
PubYear 2001
MedlineTA Cell Growth Differ
MedLine Reference 11331246:1274
Sentence Reversal of the MDM2-mediated inhibition of p53 acetylation by ARF without a detectable dissociation of the MDM2-p53 complex would be consistent with such a possibility (62) .
CellLineName saos-2

TextRef info:pmid/11861407#body:274
PubYear 2002
MedlineTA Cancer Res
MedLine Reference 11861407:1273
Sentence Therefore, induction of p53 in cells overexpressing the growth-inhibitory Mdm2 variants is not likely to be attributable to their ability to directly inhibit p53 ubiquitination by full-length Mdm2.

TextRef info:pmid/14707285#body:83
PubYear 2003
MedlineTA Mol Cancer Res
MedLine Reference 14707285:1082
Sentence This is particularly interesting given that ARF blocks the ubiquitination of p53 by MDM2 and is consistent with the idea that SUMO and ubiquitin modifications may be mutually exclusive and/or antagonistic.

TextRef info:pmid/18541670#body:191
PubYear 2008
MedlineTA Mol Cell Biol
MedLine Reference 18541670:1190
Sentence Therefore, the point mutations in the Nbs1 binding domain that inhibited Mdm2-Nbs1 association did not disrupt the interaction of Mdm2 with ARF or the ability of Mdm2 to ubiquitinate p53.

TextRef info:pmid/15933712#body:119
PubYear 2005
MedlineTA EMBO J
MedLine Reference 15933712:1118
Sentence Indeed, the stability of the tumor suppressor is mainly controlled by MDM2, which ubiquitinates p53 at these residues, thereby targeting it for degradation (Michael and Oren, 2003).
CellLineName H1299

TextRef info:pmid/12832479#body:234
PubYear 2003
MedlineTA Mol Cell Biol
MedLine Reference 12832479:1233
Sentence In summary, our data uncover the central acidic domain of MDM2 as an additional essential contributor, apart from the ring-finger domain, to MDM2-dependent p53 ubiquitination.
TextMods 41: 'AD ' -> 'acidic domain ' 118: 'RFD' -> 'ring-finger domain'
Organ Fingers

TextRef info:pmid/17189186#body:116
PubYear 2006
MedlineTA Mol Cell
MedLine Reference 17189186:1115
Sentence The major sites for p53 ubiquitination by Mdm2 are located at its C terminus, and acetylation of these residues during times of cell stress serves to block protein degradation and stabilize p53.

TextRef info:pmid/15958581#body:264
PubYear 2005
MedlineTA Cancer Res
MedLine Reference 15958581:1263
Sentence B, Western blot analysis for total p53, p53 phosphorylated on Ser15, p21Waf1/Cip1 and MDM2 in MCF-7 cells treated with 0.4 µmol/L aminoflavone for the indicated times..
CellLineName MCF7

TextRef info:pmid/17110929#body:54
PubYear 2006
MedlineTA EMBO J
MedLine Reference 17110929:1053
Sentence However, MDMX forms a heterodimer with MDM2 through C-terminal RING domains (Sharp et al, 1999; Tanimura et al, 1999), and stimulates the ability of MDM2 to ubiquitinate and degrade p53 (Gu et al, 2002; Linares et al, 2003).

TextRef info:pmid/10822382#body:146
PubYear 2000
MedlineTA Oncogene
MedLine Reference 10822382:1145
Sentence Peptide 3 blocks Mdm2-dependent p53 ubiquitination in vitro . p14ARF activates p53-dependent transcription and has been reported to block Mdm2-mediated ubiquitination of p53 (Honda and Yasuda, 1999).

TextRef info:pmid/14966292#body:280
PubYear 2004
MedlineTA Mol Cell Biol
MedLine Reference 14966292:1279
Sentence The present model is that ARF stabilizes p53 by targeting MDM2 to the nucleolus and blocking p53 ubiquitination by MDM2 (reviewed in reference 43).
CellLineName M1
CellType Epithelial Cells
Organ Mammary Gland

TextRef info:pmid/11238917#body:65
PubYear 2001
MedlineTA Mol Cell Biol
MedLine Reference 11238917:1064
Sentence If left unimpeded, mdm2 inhibits p53 function both by binding and by blocking p53's transcriptional activation domain as well as by catalyzing p53's ubiquitination, thus leading to its proteasomal degradation (32).

TextRef info:pmid/15064742#body:28
PubYear 2004
MedlineTA Oncogene
MedLine Reference 15064742:1027
Sentence Although regulation of p53 ubiquitination by MDM2 and other factors has been intensively studied, the exact mechanism by which p53, and polyubiquitinated substrates in general, are recognized by the proteasome, remains unclear.