Phospho-MDM2 (S166) Recombinant Rabbit Monoclonal Antibody [JE64-20]

Function

This gene encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. This gene is itself transcriptionally-regulated by p53. Overexpression or amplification of this locus is detected in a variety of different cancers. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in a multitude of transcript variants, many of which may be expressed only in tumor cells.

Background References

1. Qin JJ. et. al. Natural products targeting the p53-MDM2 pathway and mutant p53: Recent advances and implications in cancer medicine. Genes Dis. 2018 Jul 20;5(3):204-219.

2. Wienken M. et. al. Mdm2 as a chromatin modifier. J Mol Cell Biol. 2017 Feb 1;9(1):74-80.

Sequence Similarity

Belongs to the MDM2/MDM4 family.

Tissue Specificity

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.

Post-translational Modification

Phosphorylation on Ser-166 by SGK1 activates ubiquitination of p53/TP53. Phosphorylated at multiple sites near the RING domain by ATM upon DNA damage; this prevents oligomerization and E3 ligase processivity and impedes constitutive p53/TP53 degradation.; Autoubiquitination leads to proteasomal degradation; resulting in p53/TP53 activation it may be regulated by SFN. Also ubiquitinated by TRIM13. Deubiquitinated by USP2 leads to its accumulation and increases deubiquitination and degradation of p53/TP53. Deubiquitinated by USP7 leading to its stabilization.

Subcellular Location

Nucleus, nucleoplasm, nucleolus, cytoplasm.

UNIPROT

SwissProt: Q00987 Human

SwissProt: P23804 Mouse

Synonyms