MDM2, a ubiquitin ligase for p53, plays a central role in regulation of the stability of p53 . Akt-mediated phosphorylation of MDM2 at Ser166 and Ser186 increases its interaction with p300, allowing MDM2-mediated ubiquitination and degradation of p53 . Phosphorylation of MDM2 also blocks its binding to p19ARF, increasing the degradation of p53 .Haupt, Y. et al. (1997) Nature 387, 296-299. Mayo, L.D. and Donner, D.B. (2001) Proc. Natl. Acad. Sci. USA 98, 11598-11603. Zhou, B. P. et al. (2001) Nat. Cell Biol. 3, 973-981. Grossman, S. R. et al. (1998) Mol. Cell 2, 405-415.
Host
Rabbit
Immunogen
Peptide sequence around aa.18~22(Q-I-P-A-S) derived from Human MDM2.
Involvement In Disease
Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.
Raised In
Rabbit
Reactivity
Human
Regulatory
RUO
Relevance
MDM2, a ubiquitin ligase for p53, plays a central role in regulation of the stability of p53 . Akt-mediated phosphorylation of MDM2 at Ser166 and Ser186 increases its interaction with p300, allowing MDM2-mediated ubiquitination and degradation of p53 . Phosphorylation of MDM2 also blocks its binding to p19ARF, increasing the degradation of p53 .
Haupt, Y. et al. (1997) Nature 387, 296-299. Mayo, L.D. and Donner, D.B. (2001) Proc. Natl. Acad. Sci. USA 98, 11598-11603. Zhou, B. P. et al. (2001) Nat. Cell Biol. 3, 973-981. Grossman, S. R. et al. (1998) Mol. Cell 2, 405-415.
Species
Homo Sapiens (Human)
Specificity
The antibody detects endogenous levels of total MDM2 protein.
E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation
Ubiquitous. Isoform Mdm2-A, isoform Mdm2-B, isoform Mdm2-C, isoform Mdm2-D, isoform Mdm2-E, isoform Mdm2-F and isoform Mdm2-G are observed in a range of cancers but absent in normal tissues.
Buffer
Supplied at 1.0mg/mL in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Form
Supplied at 1.0mg/mL in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Format
liquid
Purification
Antibodies were produced by immunizing rabbits with synthetic peptide and KLH conjugates. Antibodies were purified by affinity-chromatography using epitope-specific peptide.
Purity
Antibodies were produced by immunizing rabbits with synthetic peptide and KLH conjugates. Antibodies were purified by affinity-chromatography using epitope-specific peptide.
Storage
Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.