MDM4 Recombinant Protein

This gene encodes a nuclear protein that contains a p53 binding domain at the N-terminus and a RING finger domain at the C-terminus, and shows structural similarity to p53-binding protein MDM2. Both proteins bind the p53 tumor suppressor protein and inhibit its activity, and have been shown to be overexpressed in a variety of human cancers. However, unlike MDM2 which degrades p53, this protein inhibits p53 by binding its transcriptional activation domain. This protein also interacts with MDM2 protein via the RING finger domain, and inhibits the latter's degradation. So this protein can reverse MDM2-targeted degradation of p53, while maintaining suppression of p53 transactivation and apoptotic functions. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2011]

Function: Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions. Ref.9 Ref.10

Subunit structure: Interacts with MDM2, TP53, TP73 and USP2. Found in a trimeric complex with UPB2, MDM2 and MDM4. Interacts (phosphorylated) with YWHAG; negatively regulates MDM4 activity toward TP53. Ref.9 Ref.10 Ref.11

Subcellular location: Nucleus.

Tissue specificity: Expressed in all tissues tested with high levels in thymus.

Induction: Down-regulated by cisplatin (at protein level). Ref.11

Domain: Region I is sufficient for binding TP53 and inhibiting its G1 arrest and apoptosis functions. It also binds TP73. Region II contains most of a central acidic region and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc mediates the heterooligomerization with MDM2.

Post-translational modification: Phosphorylated. Phosphorylation at Ser-367 promotes interaction with YWHAG and subsequent ubiquitination and degradation. Phosphorylation at Ser-342 also induces ubiquitination and degradation but to a lower extent. Ref.9 Ref.10Ubiquitinated and degraded by MDM2. Deubiquitination by USP2 on the other hand stabilizes the MDM4 protein. Ref.9 Ref.11

Sequence similarities: Belongs to the MDM2/MDM4 family.Contains 1 RanBP2-type zinc finger.Contains 1 RING-type zinc finger.Contains 1 SWIB domain.

Mass spectrometry: Molecular mass is 54863.3 Da from positions 1 - 490. Determined by MALDI. Ref.12