MicroRNA-34a modulates MDM4 expression via a target site in the open reading frame.

ABSTRACT:

Background

MDM4, also called MDMX or HDMX in humans, is an important negative regulator of the p53 tumor suppressor. MDM4 is overexpressed in about 17% of all cancers and more frequently in some types, such as colon cancer or retinoblastoma. MDM4 is known to be post-translationally regulated by MDM2-mediated ubiquitination to decrease its protein levels in response to genotoxic stress, resulting in accumulation and activation of p53. At the transcriptional level, MDM4 gene regulation has been less clearly understood. We have reported that DNA damage triggers loss of MDM4 mRNA and a concurrent increase in p53 activity. These experiments attempt to determine a mechanism for down-regulation of MDM4 mRNA.

Methodology/principal findings

Here we report that MDM4 mRNA is a target o

SUBMITTER: Mandke P 

PROVIDER: S-EPMC3411609 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature