Anti-Phospho-MDM2 S185 Antibody

MDM2 is a nuclear phosphoprotein with an apparent molecular mass of 90 kD that forms a complex with the p53 tumor suppressor protein. Human MDM2 was identified as a homologous product of the 'murine double minute 2' gene (mdm2) . The MDM2 gene enhances the tumorigenic potential of cells when it is overexpressed and encodes a putative transcription factor. Forming a tight complex with the p53 gene, the MDM2 oncogene can inhibit p53-mediated transactivation. MDM2 binds to p53 and amplification of MDM2 in sarcomas leads to escape from p53-regulated growth control. This mechanism of tumorigenesis parallels that for virus-induced tumors in which viral oncogene products bind to and functionally inactivate p53. Overexpression of the MDM2 oncogene was found in leukemias. Inactivation of tumor suppressor genes leads to deregulated cell proliferation and is a key factor in human tumorigenesis. MDM2 interacts physically and functionally with the retinoblastoma (RB) protein and can inhibit its growth regulatory capacity. Both RB and p53 can be subjected to negative regulation by the product of a single cellular protooncogene. The interference of binding to p53 prevents the interaction of MDM2 and its regulation of the transcriptional activity of p53 in vivo. Direct association of p53 with the cellular protein MDM2 results in ubiquitination and subsequent degradation of p53. MDM2-p53 complexes were preferentially found in S/G2M phases of the cell cycle. The MDM2 gene is alternatively spliced, producing 5 additional splice variant transcripts from the full length MDM2 gene. Four out of five of these alternatively spliced forms (MDM2a-MDMd) are missing substantial portions of the p53 binding domain and retain the acidic domain and the zinc-finger domains. The fifth and smallest transcript (MDM2e) retains the largest spliced region encoding the p53 binding domain; however, it lacks the nuclear localization signal, the acidic domain and zinc-finger domains. The alternatively spliced transcripts tend to be expressed in tumorigenic tissue, whereas the full-length MDM2 transcript is expressed in normal tissue. MDM2 is found in the nucleus and cytoplasm, however, it is expressed predominantly in the nucleoplasm. Interaction with ARF (P14) results in the localization of both proteins to the nucleus. The nucleolar localization signals in both ARF and MDM2 may be necessary to allow efficient nucleolar localization of both proteins.

MDM2 pS185, MDM-2, E3 ubiquitin-protein ligase Mdm2, p53-binding protein Mdm2, Oncoprotein Mdm2, Double minute 2 protein, RING-type E3 ubiquitin transferase Mdm2, Double minute 2 protein, Hdm2

This affinity purified antibody was prepared from whole rabbit serum produced by repeated immunizations with a synthetic peptide corresponding to an internal region near aa 175-200 of mouse MDM2.

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.

Cancer, Cell Biology, Cell Cycle, Cell Cycle Inhibitors, Epigenetics and Nuclear Signaling, Oncoproteins, Oncoproteins/Suppressors, p53 Pathway, Transcription, Ubiquitin & Ubiquitin Like Modifiers

This affinity-purified antibody is directed against the phosphorylated form of mouse MDM2 protein at the pS185 residue. The product was affinity purified from monospecific antiserum by immunoaffinity purification. Antiserum was first purified against the phosphorylated form of the immunizing peptide. The resultant affinity purified antibody was then cross-adsorbed against the non-phosphorylated form of the immunizing peptide. Reactivity occurs against Mouse MDM2 pS185 protein and the antibody is specific for the phosphorylated form of the protein. Reactivity with non-phosphorylated mouse MDM2 is minimal by ELISA and western blot. A BLAST analysis was used to suggest minimal cross-reactivity with MDM2 homologues from other sources.

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.

Store vial at -20°C prior to opening. Aliquot contents and freeze at -20°C or below for extended storage. Avoid cycles of freezing and thawing. Centrifuge product if not completely clear after standing at room temperature. This product is stable for several weeks at 4°C as an undiluted liquid. Dilute only prior to immediate use. Expiration date is one (1) year from date of opening.

Nucleus, nucleoplasm. Cytoplasm. Nucleus, nucleolus. Expressed predominantly in the nucleoplasm. Interaction with ARF (P14) results in the localization of both proteins to the nucleolus. The nucleolar localization signals in both ARF (P14) and MDM2 may be necessary to allow efficient nucleolar localization of both proteins. Colocalizes with RASSF1 isoform A in the nucleus.