MDM2 and MDM4 splicing: an integral part of the cancer spliceome

Abstract

MDM2 and MDM4, the murine double minute proteins, are oncogenes that function as important regulators of various proteins. One fundamental role for these proteins is regulation of the tumor suppressor, p53. Precise regulation of p53 is vital for coordinated malignant suppression and cell survival. Alternative splice forms of MDM2 as well as MDM4 have been associated with various cancers. Indeed, UV irradiation triggers alternative splicing of both MDM2 and MDM4. Coordinated alternative splicing in response to cellular stress or in cancerous cells regulates the posttranscriptional expression of these two genes and likely others. This concert of stress responsive mRNAs comprises the cancer spliceome and provides a fingerprint of coordinated alternative splicing in these aberrant cells. Although various transcripts have been described for both proteins, here we provide a precise catalog of the alternatively spliced transcripts of both genes and the cancers with which they are associated.