MDM2 [2A10]

GWB-1757FF

IgG2a

A549 cell lysates.

Nuclear and cytoplasmic.

0. 2% Gelatin 50mM Sodium phosphate pH 7. 5 with 0. 1% sodium azide as preservative

55 kDa). Not tested in other applications. Optimal dilutions/concentrations should be determined by the researcher. 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 also binds to p53 protein. Inactivation of tumor suppressor genes leads to deregulated cell proliferation and is a key factor in human tumorigenesis. 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. The alternatively spliced transcripts tend to be expressed in tumorigenic tissue whereas the full length MDM2 transcript is expressed in normal tissue.

Binds p53 p73 ARF(P14) ribosomal protein L5 and specifically to RNA. Can interact also with retinoblastoma protein (RB) E1A-associated protein EP300 and the E2F1 transcription factor. Forms a ternary complex with TP53/p53 and WWOX. Interacts with CDKN2AIP MTBP TBRG1 USP7 PYHIN1 and UBXN6. Isoform Mdm2-F does not interact with TP53/p53. Interacts with and ubiquitinates HIV-1 Tat.

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.

Region I is sufficient for binding p53 and inhibiting its G1 arrest and apoptosis functions. It also binds p73 and E2F1. Region II contains most of a central acidic region required for interaction with ribosomal protein L5 and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc interacts specifically with RNA whether or not zinc is present and mediates the heterooligomerization with MDM4. It is also essential for its ubiquitin ligase E3 activity toward p53 and itself.

Auto-ubiquitinated; which leads to proteasomal degradation.

MDM2 RING finger mutations that failed to ubiquitinate p53 in vitro did not target p53 for degradation when expressed in cells.

Contains 1 RanBP2-type zinc finger.

Contains 1 SWIB domain.