Ignet

Gene Information

Gene symbol: MDM2

Gene name: Mdm2, p53 E3 ubiquitin protein ligase homolog (mouse)

HGNC ID: 6973

Synonyms: HDM2, HDMX, MGC5370

Related Genes

#	Gene Symbol	Number of hits
1	AKT1	1 hits
2	ATIC	1 hits
3	BAX	1 hits
4	BCL2	1 hits
5	BRCA1	1 hits
6	CASP3	1 hits
7	CAV1	1 hits
8	CDK2	1 hits
9	CDK4	1 hits
10	CDKN1A	1 hits
11	CDKN1B	1 hits
12	CDKN2A	1 hits
13	CDKN2B	1 hits
14	CDKN2C	1 hits
15	EGR1	1 hits
16	GFAP	1 hits
17	INS	1 hits
18	MAP1LC3A	1 hits
19	MYC	1 hits
20	NEDD4	1 hits
21	PARP1	1 hits
22	PRKAA1	1 hits
23	PSMD9	1 hits
24	PTRF	1 hits
25	RB1	1 hits
26	RBL1	1 hits
27	RBL2	1 hits
28	RNF123	1 hits
29	RPS27A	1 hits
30	SIRT1	1 hits
31	TNF	1 hits
32	TP53	1 hits
33	TSPYL2	1 hits

Related Sentences

#	PMID	Sentence
1	11431698	Genetic interactions between tumor suppressors Brca1 and p53 in apoptosis, cell cycle and tumorigenesis.
2	11431698	The p53 protein regulates Brca1 transcription both in vitro and in vivo, and Brca1 participates in p53 accumulation after gamma-irradiation through regulation of its phosphorylation and Mdm2 expression.
3	15140202	Transcripts of both O-GlcNAc transferase and O-GlcNAcase are very abundant in the brain, with the highest concentrations in hippocampal neurons and Purkinje cells.
4	15140202	Cerebral proteasome function is reduced and ubiquitin and p53 accumulate in these brain regions, with the subsequent activation of a p53-dependent transgene and the endogenous Mdm2 gene.
5	15746249	Tumor necrosis factor-{alpha} decreases Akt protein levels in 3T3-L1 adipocytes via the caspase-dependent ubiquitination of Akt.
6	15746249	TNF-alpha is a mediator of insulin resistance in sepsis, obesity, and type 2 diabetes and is known to impair insulin signaling in adipocytes.
7	15746249	In the present study we examined the posttranslational mechanisms by which short-term (<6-h) exposure of 3T3-L1 adipocytes to TNF-alpha decreases Akt levels.
8	15746249	TNF-alpha treatment both increased the ubiquitination of Akt and decreased its protein level.
9	15746249	The decrease in protein was associated with the presence of an (immunoreactive) Akt fragment after TNF-alpha treatment, indicative of Akt cleavage.
10	15746249	The caspase-6 inhibitor Z-Val-Glu(OMe)-Ile-Asp(OMe)-CH(2)F potently suppressed Akt ubiquitination, degradation, and fragment formation, whereas the proteasome inhibitor Z-Leu-Leu-Leu-CHO modestly attenuated the decline in Akt levels.
11	15746249	Exposure to TNF-alpha also enhanced the association of Akt with an E3 ligase activity.
12	15746249	Adipocytes preexposed to TNF-alpha for 5 h and then stimulated with insulin for 30 min exhibited decreased levels of Akt, phosphorylated Akt, as well as phosphorylated Mdm2, which is a known direct substrate of Akt, and glucose uptake.
13	15746249	Collectively, our results suggest that TNF-alpha induces the caspase-dependent degradation of Akt via the cleavage and ubiquitination of Akt, which results in its degradation through the 26S proteasome.
14	15746249	Furthermore, the caspase- and proteasome-mediated degradation of Akt due to TNF-alpha exposure leads to impaired Akt-dependent insulin signaling in adipocytes.
15	15746249	These findings expand the mechanism by which TNF-alpha impairs insulin signaling.
16	15800711	The aim of our study was to determine whether synthetic ligands of PPARalpha and PPARgamma could affect the viability, proliferation, differentiation, apoptosis and expression of some cell cycle related proteins in glial tumor cell lines.
17	15800711	Cell lines were treated by ligands of PPARalpha (bezafibrate, gemfibrozil) and PPARgamma (ciglitazone).
18	15800711	The synthetic ligands significantly reduced or induced the expression of cyclins, p27Kip1, p21Waf1/Cip1, MDM-2, Bcl-2, Bax, PARP, Caspase 3, androgen receptors, etc. and did not affect the expression of the differentiation marker GFAP.
19	16380478	Evaluation of beta-cell replication in mice transgenic for hepatocyte growth factor and placental lactogen: comprehensive characterization of the G1/S regulatory proteins reveals unique involvement of p21cip.
20	16380478	We hypothesized that combined transgenic overexpression of hepatocyte growth factor (HGF) and placental lactogen in islets would lead to even greater increases in beta-cell mass and replication than either growth factor alone.
21	16380478	We therefore performed the first comprehensive G(1)/S cell cycle survey in islets, cataloguing the broad range of kinases, cyclins, and kinase inhibitors that control the G(1)/S transition in islets from normal, HGF, placental lactogen, and doubly transgenic mice.
22	16380478	Many of the G(1)/S checkpoint regulators (E2Fs; pRb; p107; p130; cyclins D(1),(2),(3), A, and E; cdk-2; cdk-4; p15; p16; p18; p19; p21; p27; MDM2; p53; c-Myc; and Egr-1) are present in the murine islet.
23	16380478	Most of these proteins were unaltered by overexpression of HGF or placental lactogen, either alone or in combination.
24	16380478	In contrast, p21(cip) was uniquely, dramatically, and reproducibly upregulated in placental lactogen and HGF islets. p21(cip) was also present in, and upregulated in, proliferating human islets, localizing specifically in beta-cells and translocating to the nucleus on mitogenic stimulation.
25	16380478	Homozygous p21(cip) loss releases islets from growth inhibition, markedly enhancing proliferation in response to HGF and placental lactogen.
26	17317670	Antiproliferative autoantigen CDA1 transcriptionally up-regulates p21(Waf1/Cip1) by activating p53 and MEK/ERK1/2 MAPK pathways.
27	17317670	Here we show that CDA1-induced arrest of cell growth is accompanied by increases in protein and mRNA levels of the cyclin-dependent kinase (Cdk) inhibitor protein, p21(Waf1/Cip1) (p21).
28	17317670	Both p21 induction and cell growth arrest are reversed when CDA1 expression is inhibited.
29	17317670	CDA1 also increases p53 protein, but not its mRNA, in a time- and dose-dependent manner.
30	17317670	MDM2, a ubiquitin ligase regulating p53 degradation, is inactivated by CDA1, suggesting that p53 protein accumulation is due to decreased protein degradation.
31	17317670	Knockdown of p53, using siRNA targeting two sites of p53 mRNA, abrogates transcriptional induction of p21 by CDA1.
32	17317670	Deletion of the p53 responsive element in the distal region of p21 promoter attenuates promoter activity in response to CDA1.
33	17317670	DNA damage caused by camptothecin treatment increases mRNA and protein levels of CDA1, accompanied by induction of p53.
34	17317670	The DNA damage-induced p53 induction is markedly attenuated by CDA1 knockdown.
35	17317670	CDA1 induces phosphorylation of ERK1/2(p44/42), an activity blocked by PD98059 and U0126, inhibitors of the upstream kinase MEK1/2.
36	17317670	The MEK inhibitors also block induction of p21 mRNA and abrogate p21 promoter activity stimulated by CDA1.
37	17317670	Cell cycle kinases, Cdk1, -2, -4, and -6 are inhibited by CDA1 overexpression.
38	17317670	We conclude that CDA1 induces p53- and MEK/ERK1/2 MAPK-dependent expression of p21 by acting through the p53 responsive element in the p21 promoter and that this contributes to its antiproliferative activity.
39	21085184	Using western blot analysis, we demonstrated there is upregulation of the ubiquitination ligase proteins, Nedd-4 and Mdm-2, and the lysosomal autophage protein, LC3.
40	21145380	Here, we found that iAs significantly decreased insulin secretion and cell viability, and increased ROS and MDA formation in pancreatic β-cell-derived RIN-m5F cells. iAs also induced the increases in sub-G1 hypodiploids, annexin V-Cy3 binding, and caspase-3 activity in RIN-m5F cells, indicating that iAs could induce β-cell apoptosis.
41	21145380	Moreover, iAs induced MAPKs activation, mitochondria dysfunction, p53 up-regulation, Bcl-2 and Mdm-2 down-regulation, PARP, and caspase cascades, which displayed features of mitochondria-dependent apoptotic signals.
42	21145380	In addition, exposure of RIN-m5F cells to iAs, could trigger ER stress as indicated by the enhancement in ER stress-related molecules induction (such as GRP78, GRP94, CHOP, and XBP1), procaspase-12 cleavage, and calpain activation.
43	21945951	The activation of the p53 pathway by the AMP mimetic AICAR is reduced by inhibitors of the ATM or mTOR kinases.
44	21945951	A reduced supply of energy at the cellular level leads to an increased concentration of AMP, which, in turn, results in LKB1-mediated activation of the AMPK kinase.
45	21945951	The activation of the p53 tumor suppressor protein by metabolic stress has been shown to be mediated by AMPK.
46	21945951	We showed that AICAR activated the p53 pathway in LKB1-deficient cells.
47	21945951	In cells with ATM expression silenced by shRNA, AICAR-induced p53 phosphorylation at Ser(15) and Ser(37) was attenuated.
48	21945951	Furthermore, p53 activation by AICAR was blocked by rapamycin, a specific inhibitor of the mTOR kinase, which is a crucial regulator of cell growth.
49	21945951	Rapamycin did not block p53 activation by resveratrol, which, in contrast to AICAR, induced the DNA damage response, senescence-like growth inhibition, a high level of post-translational modification of p53, and weak upregulation of MDM2 (the negative regulator of p53).
50	21945951	Thus, ATM and mTOR participate in the activation of p53 in response to a compound mimicking metabolic stress.
51	22378745	AMP-activated protein kinase (AMPK) and the NAD(+)-dependent histone/protein deacetylase sirtuin 1 (SIRT1) are metabolic sensors that can increase each other's activity.
52	22378745	In these situations, the abundance of the tumor suppressor p53 is increased; however, the relevance of this to the changes in AMPK and SIRT1 is not known.
53	22378745	Metformin induced activation of AMPK and SIRT1 and decreased p53 protein abundance.
54	22378745	It also decreased triglyceride accumulation and cytosolic oxidative stress (a trigger for p53 accumulation) and increased the deacetylation of p53 at a SIRT1-targeted site.
55	22378745	The decrease in p53 abundance caused by metformin was abolished by inhibition of murine double minute 2 (MDM2), a ubiquitin ligase that mediates p53 degradation, as well as by overexpression of a dominant-negative AMPK or a shRNA-mediated knockdown of SIRT1.
56	22378745	In addition, overexpression of p53 decreased SIRT1 gene expression and protein abundance, as well as AMPK activity in metformin-treated cells.
57	22378745	Collectively, these findings suggest the existence of a novel reciprocal interaction between AMPK/SIRT1 and p53 that may have implications for the pathogenesis and treatment of metabolic diseases.
58	23615706	To address this issue, we have used the cis-imidazoline compound Nutlin-3, an inhibitor of MDM2/p53 interaction, which represents a potent and selective non-genotoxic activator of the p53 pathway both in in vivo and in vitro experimental settings.
59	23615706	In addition, STZ alone promoted a marked decrease in the levels of several circulating cytokines, including interleukin-12 (IL-12)p40.
60	23941874	Caveolin-1/PTRF upregulation constitutes a mechanism for mediating p53-induced cellular senescence: implications for evidence-based therapy of delayed wound healing in diabetes.
61	23941874	Moreover, the ability of PDGF to promote cell proliferation/migration and regulate the phosphorylation-dependent activation of Akt and ERK1/2 appears to be attenuated as a function of diabetes.
62	23941874	Mechanistically, we found that diabetes-induced oxidative stress upregulated caveolin-1 (Cav-1) and PTRF expression, which in turn sequestered Mdm2 away from p53.
63	23941874	This process resulted in the activation of a p53/p21-dependent pathway and the induction of premature senescence in DFs.
64	23941874	Intriguingly, we confirmed that the targeted depletion of Cav-1 or PTRF using siRNA- or Vivo-Morpholino antisense-based gene therapy markedly inhibited diabetes/oxidative stress-induced premature senescence and also accelerated tissue repair in this disease state.