The p53–Mdm2 module and the ubiquitin system

Surfing the p53 network

2000 • 6,487 citations

Mdm2 promotes the rapid degradation of p53

1997 • 4,336 citations

The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53

1990 • 3,896 citations

Participation of p53 protein in the cellular response to DNA damage.

1991 • 3,818 citations

Regulation of p53 stability by Mdm2

1997 • 3,238 citations

The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation

1992 • 3,110 citations

The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53

1993 • 2,329 citations

DNA Damage-Induced Phosphorylation of p53 Alleviates Inhibition by MDM2

1997 • 2,089 citations

Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53

1997 • 1,906 citations

The p53-mdm-2 autoregulatory feedback loop.

1993 • 1,795 citations

Recognition of the polyubiquitin proteolytic signal

2000 • 1,651 citations

ARF Promotes MDM2 Degradation and Stabilizes p53: ARF-INK4a Locus Deletion Impairs Both the Rb and p53 Tumor Suppression Pathways

1998 • 1,584 citations

The Ink4a Tumor Suppressor Gene Product, p19Arf, Interacts with MDM2 and Neutralizes MDM2's Inhibition of p53

1998 • 1,538 citations

Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53

1995 • 1,401 citations

The p53 pathway

1999 • 1,322 citations

The complexity of p53 modulation: emerging patterns from divergent signals

1998 • 1,319 citations

mdm2 expression is induced by wild type p53 activity.

1993 • 1,286 citations

Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53

1995 • 1,263 citations

A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus

2001 • 1,180 citations

The alternative product from the human CDKN2A locus, p14ARF, participates in a regulatory feedback loop with p53 and MDM2

1998 • 1,152 citations

Mdm2 Is a RING Finger-dependent Ubiquitin Protein Ligase for Itself and p53

2000 • 1,026 citations

Nucleolar Arf sequesters Mdm2 and activates p53

1999 • 937 citations

HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation

2001 • 931 citations

Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2

1998 • 906 citations

UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells.

1984 • 874 citations

Ubiquitin-mediated proteolysis: biological regulation via destruction

2000 • 839 citations

DNA damage induces phosphorylation of the amino terminus of p53

1997 • 829 citations

p53

2000 • 785 citations

Association of p19ARF with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53

1999 • 731 citations

A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking

1999 • 727 citations

ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage

2001 • 681 citations

The ARF/p53 pathway

2000 • 647 citations

In vivo ubiquitination and proteasome-mediated degradation of p53(1).

1996 • 643 citations

MDM2 — master regulator of the p53 tumor suppressor protein

2000 • 637 citations

The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases

2000 • 634 citations

Nucleo-cytoplasmic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein

1998 • 610 citations

Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage

1999 • 570 citations

P19 ^ARF stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2

1999 • 543 citations

MEKK1/JNK signaling stabilizes and activates p53

1998 • 521 citations

Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53

2001 • 505 citations

Caenorhabditis elegans p53: Role in Apoptosis, Meiosis, and Stress Resistance

2001 • 457 citations

Regulation of p53 Function and Stability by Phosphorylation

1999 • 443 citations

Multiple C-Terminal Lysine Residues Target p53 for Ubiquitin-Proteasome-Mediated Degradation

2000 • 383 citations

Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase

2000 • 378 citations

A p53 Amino-Terminal Nuclear Export Signal Inhibited by DNA Damage-Induced Phosphorylation

2001 • 375 citations

Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated degradation of p53

1999 • 366 citations

Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2

1999 • 362 citations

Stress Signals Utilize Multiple Pathways To Stabilize p53

2000 • 355 citations

The MDM2 RING-finger domain is required to promote p53 nuclear export

2000 • 352 citations

The hPLIC Proteins May Provide a Link between the Ubiquitination Machinery and the Proteasome

2000 • 348 citations

Mutations in Human ARF Exon 2 Disrupt Its Nucleolar Localization and Impair Its Ability to Block Nuclear Export of MDM2 and p53

1999 • 343 citations

JNK targets p53 ubiquitination and degradation in nonstressed cells

1998 • 339 citations

Multiple roles of the tumor suppressor p53

2002 • 335 citations

An intact HDM2 RING-finger domain is required for nuclear exclusion of p53

2000 • 330 citations

Regulation of p53 Function

2001 • 319 citations

Proteolytic Cleavage of Human p53 by Calpain: a Potential Regulator of Protein Stability

1997 • 305 citations

The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes.

1994 • 300 citations

DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization

1999 • 296 citations

Stabilization of the MDM2 Oncoprotein by Interaction with the Structurally Related MDMX Protein

1999 • 282 citations

The p53 and Mdm2 families in cancer

2002 • 281 citations

Accumulation of p53 in a mutant cell line defective in the ubiquitin pathway.

1994 • 274 citations

SUMO-1 Modification of Mdm2 Prevents Its Self-Ubiquitination and Increases Mdm2 Ability to Ubiquitinate p53

2000 • 271 citations

An N-terminal p14ARF peptide blocks Mdm2-dependent ubiquitination in vitro and can activate p53 in vivo

2000 • 257 citations

Stabilization of p53 by p14ARF without relocation of MDM2 to the nucleolus

2001 • 255 citations

RB Regulates the Stability and the Apoptotic Function of p53 via MDM2

1999 • 255 citations

The mdm-2 gene is induced in response to UV light in a p53-dependent manner.

1993 • 250 citations

C-Terminal Ubiquitination of p53 Contributes to Nuclear Export

2001 • 241 citations

Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms

2001 • 230 citations

Virus-mediated killing of cells that lack p53 activity

2001 • 201 citations

Regulation of Mdm2-Directed Degradation by the C Terminus of p53

1998 • 194 citations

Nuclear localization is essential for the activity of p53 protein.

1991 • 190 citations

Identification of a cryptic nucleolar-localization signal in MDM2

2000 • 186 citations

Physical association of ubiquitin ligases and the 26S proteasome

2000 • 178 citations

Different effects of p14ARF on the levels of ubiquitinated p53 and Mdm2 in vivo

2001 • 172 citations

The MDM2 Oncoprotein Binds Specifically to RNA through its RING Finger Domain

1996 • 170 citations

Human mdm2 Mediates Multiple Mono-ubiquitination of p53 by a Mechanism Requiring Enzyme Isomerization

2001 • 166 citations

Mdm2: the ups and downs.

1999 • 165 citations

Proteolysis by Calpains: a Possible Contribution to Degradation of p53

1997 • 162 citations

A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control

2001 • 156 citations

mdm2 and bax, downstream mediators of the p53 response, are degraded by the ubiquitin-proteasome pathway.

1998 • 153 citations

Mdm2: The Ups and Downs

1999 • 148 citations

Hdmx Stabilizes Mdm2 and p53

2000 • 145 citations

p53 Accumulation, defective cell proliferation, and early embryonic lethality in mice lacking tsg101

2001 • 142 citations

Novel phosphorylation sites of human tumour suppressor protein p53 at Ser20 and Thr18 that disrupt the binding of mdm2 (mouse double minute 2) protein are modified in human cancers

1999 • 138 citations

The loss of mdm2 induces p53 mediated apoptosis

2000 • 137 citations

Cocompartmentalization of p53 and Mdm2 Is a Major Determinant for Mdm2-Mediated Degradation of p53

2001 • 125 citations

Oligomerization Is Required for p53 to be Efficiently Ubiquitinated by MDM2

1999 • 122 citations

MDM2-dependent ubiquitination of nuclear and cytoplasmic P53

2000 • 119 citations

The death substrate Gas2 binds m-calpain and increases susceptibility to p53-dependent apoptosis

2001 • 109 citations

Anti-apoptotic activity of low levels of wild-type p53.

1996 • 109 citations

c-Abl Neutralizes the Inhibitory Effect of Mdm2 on p53

1999 • 104 citations

Analysis of the degradation function of Mdm2.

1999 • 104 citations

MDM2: life without p53

2001 • 98 citations

Deregulation of the ubiquitin system and p53 proteolysis modify the apoptotic response in B-CLL lymphocytes

2000 • 98 citations

MDM2 and MDMX can interact differently with ARF and members of the p53 family

2001 • 97 citations

Nuclear degradation of p53 occurs during down‐regulation of the p53 response after DNA damage

2002 • 92 citations

A model for tumor suppression using H-1 parvovirus.

1993 • 90 citations

The contribution of the acidic domain of MDM2 to p53 and MDM2 stability

2001 • 88 citations

On the involvement of calpains in the degradation of the tumor suppressor protein p53

1997 • 85 citations

p53 Activation by Nitric Oxide Involves Down-regulation of Mdm2

2002 • 85 citations

ATM complexes with HDM2 and promotes its rapid phosphorylation in a p53-independent manner in normal and tumor human cells exposed to ionizing radiation

2000 • 65 citations

Multiple sites of in vivo phosphorylation in the MDM2 oncoprotein cluster within two important functional domains

2000 • 61 citations

Mdm2 Mutant Defective in Binding p300 Promotes Ubiquitination but Not Degradation of p53

2001 • 56 citations

Downregulation of MDM2 stabilizes p53 by inhibiting p53 ubiquitination in response to specific alkylating agents

2001 • 43 citations

Phosphorylation of murine double minute clone 2 (MDM2) protein at serine-267 by protein kinase CK2 in vitro and in cultured cells

2001 • 43 citations

Stabilization and Activation of p53 by the Coactivator Protein TAFII31

2001 • 41 citations

Novel phosphorylation sites of human tumour suppressor protein p53 at Ser20 and Thr18 that disrupt the binding of mdm2 (mouse double minute 2) protein are modified in human cancers

1999 • 39 citations

Polyoma virus disrupts ARF signaling to p53

2001 • 33 citations

Characterization of sequence elements involved in p53 stability regulation reveals cell type dependence for p53 degradation

1998 • 30 citations