Mdm4: don't judge an isoform by its mRNA levels!

Bardot, Boris; Toledo, Franck

doi:10.18632/aging.100826

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2021

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“…As with MDM4-S, a splicing change need not result in the expression of a novel protein in order to have a biological impact [ 31 ]. The diversion of MDM4 pre-mRNA away from the full-length isoform and toward unstable isoforms such as MDM4-S could reduce total MDM4 protein available to inhibit p53, allowing MDM4-S to lead to p53 activation.…”

Section: Discussionmentioning

confidence: 99%

MDM4 Isoform Expression in Melanoma Supports an Oncogenic Role for MDM4-A

Alatawi

Kho

Markey

2021

Journal of Skin Cancer

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The p53 tumor suppressor integrates upstream signals such as DNA damage and active oncogenes to initiate cell cycle arrest or apoptosis. This response is critical to halting inappropriate growth signals. As such, p53 activity is lost in cancer. In melanoma, however, the p53 gene is intact in a reported 94% of human cases. Rather than direct mutation, p53 is held inactive through interaction with inhibitory proteins. Here, we examine the expression of the two primary inhibitors of p53, MDM2 and MDM4, in genomic databases and biopsy specimens. We find that MDM4 is frequently overexpressed. Moreover, changes in splicing of MDM4 occur frequently and early in melanomagenesis. These changes in splicing must be considered in the design of therapeutic inhibitors of the MDM2/4 proteins for melanoma.

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Section: Discussionmentioning

confidence: 99%